2014 Practice RAC Exam

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 Notification is required when the specification range is widened. VIII. SPECIFICATIONS —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). —Moderate Changes (Supplement - Changes Being Effected) —Supplement - Changes Being Effected in 30 Days b. Relaxing an acceptance criterion

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 C. Reserve samples should be stored under conditions in line with those on the product labeling D. Any evidence of reserve sample deterioration should be investigated and documented

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

The quality assurance manager of a small company with 12 employees is the company's only internal auditor and has been performing all internal quality system audits for three years. This does not meet the requirements for performing internal quality systems audits because: A. Auditor independence has not been ensured B. There is no one in the company qualified to train the quality assurance manager in quality auditing principles C. Quality system audits cannot be performed by the same auditor for more than two audits in a row D. The Audit Reports need to be approved by a second internal auditor not involved with the specific audit

A. Auditor independence has not been ensured Auditor independence has not been ensured because the quality assurance manager is auditing areas of the quality system for which he/she is responsible. This is not permitted.

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 Response A 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 B 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 C 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 C 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 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 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.

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 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.

Which of the following is NOT required for compliance under 21 CFR Part 11 (electronic records and electronic signatures)? A. Manually generated, time-stamped audit trails to record the date and time of operator entries and actions that create, modify or delete electronic records B. Validation of systems to ensure accuracy, reliability, consistent intended performance and the ability to discern invalid or altered records C. Authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record or perform the operation at hand D. Establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification

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

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 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.

Your company recently gained approval for a novel biologic drug to treat a rare disease that has no other known therapy. The demand for your compound is several times what was anticipated and you are running into a supply issue due to the scarcity of a manufacturing component. Which manufacturing license strategy would immediately help to address the supply shortage? A. Obtain the initial and partially-manufactured version of the product from unlicensed facilities B. No immediate action is necessary until you expand your own manufacturing capabilities next year C. Share manufacturing between several manufacturers that are registered and licensed for specific aspects of the products manufacturing process D. Utilize a contract manufacturer where your company will hold the license and the contract facility will be under your control

A. Obtain the initial and partially-manufactured version of the product from unlicensed facilities -Answer A is correct because, in certain circumstances, you can work with unlicensed manufacturers to address a shortage. -Answer B is a distracter. -Answer C describes a situation where "shared manufacturing" is taking place. License applications/supplements must be filed concurrently and this process would not be considered an "immediate action." -Answer D is incorrect because contract manufacturing would not be considered the best option for "immediate action."

A drug manufacturer is assembling a clinical evaluation plan for a New Chemical Entity (NCE) to include in an IND submission. Which of the following NCE studies DOES NOT need to be included by the manufacturer in the clinical trial registry at www.clinicaltrials.gov? A. Phase 1 studies B. Phase 2 studies C. Phase 3 studies D. Phase 4 postmarketing studies

A. Phase 1 studies Clinical Trials That Must be Registered at ClinicalTrials.gov—FDAAA, Title VIII, Sec. 801 ("Applicable Clinical Trials") —Trials of drugs and biologics: controlled clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation —Trials of devices: (a) a prospective clinical study of health outcomes comparing an intervention with a device, subject to FDA regulation, against a control in human subjects, (other than small feasibility studies), and (b) pediatric postmarket surveillance

An NDA holder wants to extend the drug product shelf life from two to three years. What is the best course of action to pursue? A. Present three years of real-time stability data on three consecutive batches following an approved stability protocol in the NDA Annual Report B. Present 18 months of accelerated stability data on three consecutive batches in the NDA Annual Report C. Present three years of real-time stability data on three consecutive batches in an NDA Changes Being Effected in 30-Days supplement D. Present 18 months of accelerated stability data on three consecutive batches in a NDA Changes Being Effected in 0-Days supplement

A. Present three years of real-time stability data on three consecutive batches following an approved stability protocol in the NDA Annual Report Data from stability studies should be provided on at least three consecutive batches of the drug product. An extension of an expiration dating period based on full shelf life data on production batches obtained under a protocol approved in the application

A blood center has discovered a unit of packed red blood cells 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. 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.

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

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

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

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

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

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

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

A. Temporally associated with the use of the investigational item but are not serious and/or unexpected Events that are not undesirable are not adverse events. Events in animals are not reportable. Events of greater severity than described in the Investigator's Brochure are unexpected and therefore reportable. According to 21 CFR 312.32: Answer B should be reported 2)Unexpected fatal or life-threatening suspected adverse reaction reports . The sponsor must also notify FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than 7 calendar days after the sponsor's initial receipt of the information. Additionally, according to the Guidance Adverse Event Reporting to IRBs—Improving Human Subject Protection: An AE that is described or addressed in the investigator's brochure, protocol or Informed Consent documents, but occurs at a specificity or severity that is inconsistent with prior observations should be reported. According to 21 CFR 312.32 Answer ID 3 Should be reported: Increased rate of occurrence of serious suspected adverse reactions . The sponsor must report any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. According to 21 CFR 312.32 Answer ID 4 also should be reported: iii) Findings from animal or in vitro testing. The sponsor must report any findings from animal or in vitro testing, whether or not conducted by the sponsor, that suggest a significant risk in humans exposed to the drug, such as reports of mutagenicity, teratogenicity, or carcinogenicity, or reports of significant organ toxicity at or near the expected human exposure.

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

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 Primary mode of action is the pain drug and the device is a delivery system.

Your company would like to submit an IND for the use of a new drug on subjects with a life-threatening disease for which there are no suitable alternative drugs available. Which type of IND application would be most suitable for this type of investigation? A. Treatment IND B. Emergency Use IND C. Investigator IND D. Expanded access IND

A. Treatment IND A treatment IND would be most suitable for this application (answer 1). Treatment INDs are issued as a means of providing eligible subjects with investigational drugs or biologics for the treatment of serious and life-threatening illnesses for which there are no suitable alternative treatments.

For validated processes and systems, the possibility of revalidation should be considered for all of the following EXCEPT: A. When the manufacturer tightens the specification for container closure torque. B. Whenever there are changes in packaging, formulation, equipment, or processes which could impact product effectiveness or product characteristics C. When a change is made in raw material supplier D. Based on procedures in the Change Control Standard Operating Procedure.

A. When the manufacturer tightens the specification for container closure torque. Answers C and D are straight from the Guideline on General Principles of Process Validation, and CGMP calls for a change control process documented as an SOP as an element of the validation program.

What is the formal early collaboration meeting that was implemented through the Food and Drug Administration Modernization Act (FDAMA)? A. PDP meeting B. Agreement Meeting C. Pre-IDE meeting D. Type A meeting

B. Agreement Meeting 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.

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

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

Your company's drug product is a little yellow pill. A pharmacist tells a sales rep that several customers complained that your little yellow pill looks a lot like another other little yellow pill. One customer explained how they took the wrong pill and got very dizzy. The sales rep informs you about those complaints. How should this be reported to FDA? A. As a FIELD Alert report sent within 15 days B. As a FIELD Alert report sent within three days C. As an Annual Report D. As a distribution data report

B. As a FIELD Alert report sent within three days Rapid communication methods are utilized to provide the information the drug product has been mistaken for another article.

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 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 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 "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 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) 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.

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

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

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

B. Company X should submit an NDA containing full reports of investigations of safety and effectiveness The clinical studies were conducted by the applicant. A new dosage formulation with a new route of administration will require an NDA.

Company ABC is planning to move its manufacturing process to a new clinical manufacturing site. The product is a biologic and is currently in a Phase 2 clinical study. Once the manufacturing site is validated, it will produce material for the planned Phase 3 pivotal study. What sort of comparability data would be required for the manufacturing site change? A. Comparability data on the two processes must include analytical data and a small clinical trial to prove equivalence. B. Comparability data on the two processes will include analytical data and a nonclinical toxicology study. C. Comparability data on the two processes will include analytical data. D. Comparability is not required as the process is exactly the same.

B. Comparability data on the two processes will include analytical data and a nonclinical toxicology study. Bioanalytical data, stability studies and a nonclinical toxicology study are suggested to prove the two processes are comparable prior to starting the Phase 3 studies at the new manufacturing site.

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 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.

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. 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 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. 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).

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

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

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 cha

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. 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.

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

B. Field copy certification Field copy certification only applies to NDA products, whereas all of the others sections are requirements for both BLAs and NDAs.

You are the regulatory expert in a small start-up medical device company. A clinical investigation is required for your Class II medical device 510(k) submission. One of the investigators who conducts the study also has received 1,000 stock options from your company as part of his consulting agreement. What information related to this investigator must be included with your 510k submission? A. Form 3454, certifying lack of financial interests and arrangements B. Form 3455, disclosing the stock options for the specific investigator C. Form 3455, disclosing proprietary interest in the tested product D. No additional forms are required

B. Form 3455, disclosing the stock options for the specific investigator The guidance states if the value of stock options cannot be determined through public prices, it needs to be disclosed.

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 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 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? 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.

With regard to NDA applications, all the following are true EXCEPT: A. Labeling and promotional material must be submitted during the preapproval period B. Labeling changes are reported in the quarterly report to an approved NDA C. Fees may be waived if the designated drug is for orphan products D. NDAs may be submitted in the traditional format on paper or electronically

B. Labeling changes are reported in the quarterly report to an approved NDA Depending on the type of change, labeling changes are reported either in the Annual Report or in a supplement. (a) Changes to an approved application. (1)(i) Except as provided in paragraph (a)(1)(ii) of this section, the applicant must notify FDA about each change in each condition established in an approved application beyond the variations already provided for in the application. The notice is required to describe the change fully. Depending on the type of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c) of this section or by inclusion of the information in the annual report.

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

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

A medical device that has not been released for sale or use is shipped to a foreign distributor of Company XYZ. Company XYZ contacts the foreign distributor and the foreign distributor confirms the product is still at its warehouse in the US. Company XYZ requests the foreign distributor to return the medical device immediately. The enforcement activity described is an example of a: A. Market Withdrawal B. Stock Recovery C. Class I Recall D. Class III Recall

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

FDA has conducted an initial review of your company's PMA application and issued a set of deficiencies. A PMA amendment has been submitted to FDA in response to the deficiencies. In the meantime, FDA has requested a Panel Meeting for review of the PMA. Your company has begun preparing for the Panel Meeting. Six weeks prior to the scheduled Panel Meeting, FDA issues a letter stating the PMA is now not approvable because additional deficiencies have been identified and some of the responses to the previous deficiencies are not adequate. As the regulatory person responsible for this submission, you will direct the project team as follows: A. The Panel Meeting will occur as scheduled, so prepare for the meeting and at a later date respond to the recent deficiencies B. The Panel Meeting will be postponed until FDA receives adequate responses to the deficiencies; focus all efforts on responses to the deficiencies C. Ther

B. The Panel Meeting will be postponed until FDA receives adequate responses to the deficiencies; focus all efforts on responses to the deficiencies The Panel Meeting would not take place as scheduled because the PMA is considered nonapprovable until the deficiencies are addressed. The company has 180 days to submit an amendment to the PMA and a Panel Meeting would be rescheduled for a later date pending the company's responses to the deficiencies.

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

B. Time & Extent Application (TEA) or Citizen Petition

A company has a new blood pressure medication, NOSTRESS. The clinical trials are completed and demonstrate similar safety and efficacy to those drugs currently on the market. The clinical data are ready for submission to FDA. The Chemistry, Manufacturing and Controls data are not ready, but will be ready in two months. What is the fastest way to file this NDA? A. Submit NDA as a Rolling Review B. Wait until the CMC data are ready to submit C. File the NDA with the clinical data and update the CMC data in the four-month update D. Request Fast Track designation

B. Wait until the CMC data are ready to submit Rolling review and Fast Track are only for drugs that treat serious disease and meet an unmet medical need; the four-month safety report is for clinical safety only.

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 factor

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 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.

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 As the drug has been studied and results are published, a comparability study between IV and oral is acceptable under a 505(b)2.

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

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

A company is developing a new device, and the device classification under which it would fall is not clear. As the regulatory professional, you would make the following submission: A. 510(k) Premarket Notification B. Request for Designation C. 513(g) Request for Information D. Type A Meeting Request

C. 513(g) Request for Information —A 510(k) submission is filed when you know the classification of the device and are comparing it to a predicate device in order to obtain FDA clearance. —A Request for Designation is when you need FDA to determine whether your product is a drug, device, biological product or combination product. —A Type A Meeting is needed to help an otherwise stalled product development program proceed. —A 513(g) Request for Information is submitted to FDA as a request to determine the device classification and applicable requirements under the FD&C Act.

How many days does FDA have to review an Abbreviated 510(k)? A. 30 days B. 60 days C. 90 days D. 180 days

C. 90 days Because both Special 510(k) and Abbreviated 510(k) are alternate approaches to the Traditional 510(k), with the goal of streamlining evaluation of the application, the Special 510(k) review clock is 30 days. Many people often think the review clock for an Abbreviated 510(k) is also 30 days, but it is actually 90.

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 Any NDA or SNDA that contains new clinical data must pay a fee to FDA upon submission of the application.

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

C. Abbreviated 510(k) A manufacturer has the option to submit an Abbreviated 510(k) when FDA has recognized relevant consensus standards applicable to the device. This Abbreviated 510(k) will include a declaration of conformity to the recognized consensus standards, and this declaration, in many cases, should eliminate the need to review actual test data for those aspects of the device addressed by the standards, thus the review will be more efficient.

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 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.

You work for a company that is developing an autologous cellular therapy product. FDA informed your company that its product will be regulated as an HCT/P (Human Cells, Tissues and Cellular and Tissue-Based Product). Based on this information, with which of the following regulatory requirements will your company need to be compliant when manufacturing the product? A. 21 CFR 210 / 211 (CGMP requirements for pharmaceuticals) B. 21 CFR 2171 and 21 CFR 820 C. All Subparts of 21 CFR 1271 except Subpart C (Donor Eligibility) D. All Subparts of 21 CFR 1271

C. All Subparts of 21 CFR 1271 except Subpart C (Donor Eligibility) As the product is regulated under section 361 of the PHS Act, it is only subject to the requirements in 21 CFR 1271, with the exception of Subpart C, as autologous products are not subject to donor eligibility requirements.

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 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.

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 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 C.

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 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).

A Drug Master File may be used for any of the following purposes EXCEPT: A. Supplemental information on the drug product or drug substance B. Supplemental information for any type of submission to the agency C. FDA approval of the Drug Master File D. Incorporation by reference all or part of the contents of any Drug Master File in support of a submission when the holder has authorized the incorporation in writing

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

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 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 pharmaceutical company received approval of a drug that contains a boxed warning. 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 Answer C 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" about certain very serious drug risks."

The final authority for ensuring the adequacy of an Investigational New Drug (IND) Informed Consent Form resides with the: A. IND sponsor B. FDA C. Institutional Review Board (IRB) D. Person conducting the informed consent process with the patient

C. Institutional Review Board (IRB) Consent Document Content For studies subject to the requirements of FDA regulations, the Informed Consent documents should meet the requirements of 21 CFR 50.20 and contain the information required by each of the eight basic elements of 21 CFR 50.25(a), and each of the six elements of 21 CFR 50.25(b) appropriate to the study. IRBs have the final authority for ensuring the adequacy of the information in the Informed Consent document. The duly constituted institutional review board, described in paragraph (d)(1)(v) of this section, must review and approve: (i) The required information sheet; (ii) The adequacy of the plan to disseminate information, including distribution of the information sheet to potential recipients, on the investigational product (e.g., in forms other than written); (iii) The adequacy of the information and plans for its dissemination to health care providers, including potential side effects, contraindications, potential interactions, and other pertinent considerations; and (iv) An informed consent form as required by part 50 of this chapter, in those circumstances in which DOD determines that informed consent may be obtained from some or all personnel involved. 21 CFR 56.103 also says: a) Except as provided in 56.104 and 56.105, any clinical investigation which must meet the requirements for prior submission (as required in parts 312, 812, and 813) to the Food and Drug Administration shall not be initiated unless that investigation has been reviewed and approved by, and remains subject to continuing review by, an IRB meeting the requirements of this part. Or more generically the reference could just be to 21 CFR 56, which outlines the roles and responsibilities of an IRB.

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 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.

Postapproval pharmacovigilance for an adverse drug experience is: A. Mandatory for both manufacturers and healthcare professionals. B. Voluntary for both manufacturers and healthcare professionals. C. Mandatory for manufacturers but voluntary for healthcare professionals. D. Voluntary for manufacturers but mandatory for healthcare professionals.

C. Mandatory for manufacturers but voluntary for healthcare professionals. 21 CFR 314.80 (c)(1)(i) and (iii) MedWatch Form FDA 3500 and 3500A "(c)(1)(i) The applicant shall report each adverse drug experience that is both serious and unexpected whether foreign or domestic, as soon as possible but in no case later than 15 calendar days of initial receipt of the information by the applicant."(iii) The requirements of paragraphs (c)(1)(i) and (c)(1)(ii) of this section, concerning the submission of postmarketing 15-day Alert reports, shall also apply to any person other than the applicant (nonapplicant) whose name appears on the label of an approved drug product as a manufacturer, packer, or distributor." Sec. 314.80 Postmarketing reporting of adverse drug experiences. (c) Reporting requirements. The applicant shall report to FDA adverse drug experience information, as described in this section. (1)(i) Postmarketing 15-day "Alert reports." The applicant shall report each adverse drug experience that is both serious and unexpected, whether foreign or domestic, as soon as possible but in no case later than 15 calendar days of initial receipt of the information by the applicant. (ii) Postmarketing 15-day "Alert reports"—follow up. The applicant shall promptly investigate all adverse drug experiences that are the subject of these postmarketing 15-day Alert reports and shall submit follow up reports within 15 calendar days of receipt of new information or as requested by FDA. If additional information is not obtainable, records should be maintained of the unsuccessful steps taken to seek additional information. Postmarketing 15-day Alert reports and follow ups to them shall be submitted under separate cover. (iii) Submission of reports. The requirements of paragraphs (c)(1)(i) and (c)(1)(ii) of this section, concerning

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

C. Monoclonal antibodies for in vivo use Monoclonal antibodies for in vivo use were transferred to CDER's Office of New Drugs (OND) effective 30 June 2003.

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 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 It is the investigator's responsibility to obtain the informed consent.

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 Market withdrawal is not subject to legal action by FDA. PART 7 -- ENFORCEMENT POLICY 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.

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 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 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 A Suitability Petition is a request for permission to submit an ANDA. Sec. 314.93 Petition to request a change from a listed drug. 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.

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

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

You are assigned the task of obtaining an Orphan Drug Designation (ODD) for a novel investigational drug for new onset Type I diabetes mellitus. Which of the following is NOT among your points of consideration for this ODD application? A. The ODD application must be submitted for review to FDA Office of Orphan Products Development (OOPD) B. This investigational drug may qualify for ODD as new onset Type I diabetes mellitus may be a medically plausible disease subset under the Orphan Drug Act C. The ODD application must be submitted electronically to the OOPD through the FDA Electronic Submission Gateway (ESG) D. The scientific rationale and population prevalence are two areas of the ODD application that are most critically reviewed by FDA

C. The ODD application must be submitted electronically to the OOPD through the FDA Electronic Submission Gateway (ESG) Sponsors may send the submission directly to OOPD on physical media with a signed paper cover letter.

You work for a German-based device manufacturer that packages the device in Ireland and sells the product in the US through a US-based company. The 510(k) was written by a contract organization. The label of your product may indicate any of the following EXCEPT: A. The principal place of business in the US B. The packaging location address C. The address of the contractor who submitted the 510(k) D. The address of the distributor

C. The address of the contractor who submitted the 510(k) The address of the submitting contractor need not be listed on the final labeling of the product.

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 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 that is subject to device tracking requirements. You are required to report information to aid in the tracking to: A. FDA B. Customs Authorities C. The manufacturer D. The hospital in which the device will be used

C. The manufacturer "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..."

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

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

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. Answer C is true for Phase 2 studies Answer A is true for Phase 1 studies Answers B and D are true for Phase 3 studies.

Company ABC has requested orphan drug designation for its product. The product is currently in clinical trials for a rare blood disease for which the prevalence is approximately 100,000 individuals. The product previously approved for another indication for which the prevalence is approximately one million individuals. Would the company be eligible for orphan drug designation for the rare blood disease and why? A. No, orphan designation cannot be granted on products previously approved B. Yes, orphan designation can be granted because the product is approved C. Yes, orphan designation can be granted because it is for a different indication than the indication currently marketed D. No, orphan designation cannot be granted because the product is currently approved

C. Yes, orphan designation can be granted because it is for a different indication than the indication currently marketed A sponsor may request orphan drug designation of a previously unapproved drug, or for a new orphan indication for an already marketed drug. In addition, a sponsor of a drug that is otherwise the same drug as an already approved orphan drug may seek and obtain orphan drug designation for the subsequent drug for the same rare disease or condition if it can present a plausible hypothesis that its drug may be clinically superior to the first drug.

ABC company will be using an investigational drug product for Phase 1 clinical studies that include SAD, MAD, food effect and drug-drug-interaction studies. The investigational drug product has a potential genotoxic impurity that is currently controlled at the level of exposure of NMT 10 µg/day. After completion of Phase 1 studies, the drug is planned to be reformulated into a different dosage form and re-evaluated for safety and quality. Is the current investigational drug acceptable for Phase 1 studies? A. No, since it has a potential genotoxic impurity B. No, since the potential genotoxic impurity is above the recommended 1.5 µg/day exposure C. Yes, since duration of all indicated clinical studies is less than six months D. Yes, since it will be used in investigational studies only

C. Yes, since duration of all indicated clinical studies is less than six months Acceptable qualification thresholds of genotoxic impurities during clinical development are based on the drug`s daily intake and duration of the studies. Phase 1 clinical studies are normally short-term, single-dose studies and last no longer than 14 days (with an exception for MAD that can run longer). The 10 µg/day daily intake of genotoxic impurity can qualify up to six months. Therefore, the use of this investigational drug product for a Phase 1 study is okay. However, for longer clinical studies and commercial drug product, the company should run qualification studies or reduce the threshold to NMT 1.5 µg/day.

A company is developing a demineralized bone matrix (DBM) product intended as a bone void filler. The DBM product consists of DBM manufactured from human allograft bone and a polymer gel to improve handling and containment of the DBM in the bone defect. The DBM product must comply with the following regulation(s): A. 21 CFR 210 and 211 B. 21 CFR 820 C. 21 CFR 1271 D. 21 CFR 1271 and 820

D. 21 CFR 1271 and 820 Demineralized bone matrix alone (i.e., not combined with another component) is an HCT/P which meets the four criteria to be regulated solely under Section 361 of the Public Health Service Act. FDA, however, has determined the addition of certain components to DBM, such as polymer gels or calcium phosphates, meets the definition of a device as they are intended to affect the structure or function of the body by assisting in the filling of bone voids. These DBM products, therefore, are regulated as devices by CDRH (510(k) clearance required) and as such must comply with 21 CFR 820 Quality System Regulation. In addition, the product also needs to comply with the requirements of 21 CFR 1271 Human Cells, Tissues and Cellular and Tissue-Based Products due to the human tissue component.

A sponsor's drug development program has come to a standstill and is in need of a meeting with FDA. The company decides to schedule a meeting through an IND amendment. Within how many days of FDA receipt should the meeting be scheduled? A. 180 days B. 75 days C. 60 days D. 30 days

D. 30 days A Type A meeting is a meeting needed to help an otherwise stalled product development program proceed.These meetings, also known as "critical path" meetings, should be scheduled to occur within 30 days of FDA receipt of a written meeting request.

The difference between advertising and professional labeling for prescription drugs is: A. Advertising can be directed only to consumers and professional labeling can be directed only to professionals. B. Advertising must be accompanied by a package insert while professional labeling must be accompanied by a brief summary. C. Advertising can be directed to either consumers or professionals while professional labeling can be directed only to consumers. D. Advertising must be accompanied by a brief summary and professional labeling must be accompanied by a package insert.

D. Advertising must be accompanied by a brief summary and professional labeling must be accompanied by a package insert. Per 21 CFR 202.1, prescription drug advertisements include true statement of information in brief summary relating to side effects, contraindications and effectiveness.

Your company submitted a supplement that is subject to the Pediatric Research Equity Act (PREA). As you develop your clinical study plan, the best study design might include the following considerations, EXCEPT: A. Assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations B. Support dosing for each pediatric subpopulation for which the product has been assessed to be safe and effective C. Support drug route of administration for each pediatric subpopulation for which the product has been assessed to be safe and effective D. Compare the safety and effectiveness of the product for the claimed indications in pediatric and adult patients

D. Compare the safety and effectiveness of the product for the claimed indications in pediatric and adult patients Comparative clinical studies between adults and pediatric subjects are not a requirement for pediatric labeling and approval.

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

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

Unless exempt, all donors of human cells, tissues and cellular and tissue-based products (HCT/Ps) must be tested for RCDADs (Relevant Communicable Disease Agents and Disease), which include: A. HIV (Type 1 and Type 2), Hepatitis B, B. HIV (Type 1 and Type 2) and Treponema pallidum C. HIV (Type 1 and Type 2) and Hepatitis C D. HIV (Type 1 and Type 2), Hepatitis B, Hepatitis C and Treponema pallidum

D. HIV (Type 1 and Type 2), Hepatitis B, Hepatitis C and Treponema pallidum Per 21 CFR 1271.85, a specimen from the donor of cells or tissue, whether viable or nonviable, must be tested for evidence of infection due to relevant communicable disease agents including: HIV (Type 1 and Type 2), Hepatitis B, Hepatitis C and Treponema pallidum. Sec. 1271.85 What donor testing is required for different types of cells and tissues? —(a) All donors. To adequately and appropriately reduce the risk of transmission of relevant communicable diseases, and except as provided under 1271.90, you must test a specimen from the donor of cells or tissue, whether viable or nonviable, for evidence of infection due to relevant communicable disease agents, including: (1) Human immunodeficiency virus, type 1; (2) Human immunodeficiency virus, type 2; (3) Hepatitis B virus; (4) Hepatitis C virus; and (5)Treponema pallidum —(b) Donors of viable, leukocyte-rich cells or tissue. In addition to the relevant communicable disease agents for which testing is required under paragraph (a) of this section, and except as provided under 1271.90, (1) You must test a specimen from the donor of viable, leukocyte-rich cells or tissue to adequately and appropriately reduce the risk of transmission of relevant cell-associated communicable diseases, including: (i) Human T-lymphotropic virus, type I; and (ii) Human T-lymphotropic virus, type II. (2) You must test a specimen from the donor of viable, leukocyte-rich cells or tissue for evidence of infection due to cytomegalovirus (CMV), to adequately and appropriately reduce the risk of transmission. You must establish and maintain a standard operating procedure governing the release of an HCT/P from a donor whose specimen tests reactive for CMV. —(c) Donors of reproductive cells or tissue. In addition to

A new drug product is being considered by your company. It has been on the market for more than 30 years in a foreign country, but has never been approved in the US. In order to sell this product in the US, you may do the following immediately EXCEPT: A. Determine monograph or NDA status of the product B. Initiate clinical studies in the foreign country to support the claims since the clinical data is old and would not meet current requirements C. Determine whether this is a New Chemical Entity D. Import the product and use new labeling

D. Import the product and use new labeling The importation of a drug product to be distributed in the US must meet US regulations, regardless of its approved status in another country.

A company is planning to develop a sunscreen with an ingredient cosistent with its published monograph for marketing within the US. What type of filing does the company have to submit? A. No action is required by the sponsor as it is a cosmetic B. ANDA C. 505(b)(1) D. No premarket approval is required

D. No premarket approval is required The active ingredients allowed for use in sunscreens are published in the final monograph 21 CFR 352. A product that includes a codified sunscreen ingredient does not require premarket approval by FDA provided the full conditions of the monograph are met.

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. Nothing is required and the subject can continue in the study when recovered.

D. Nothing is required and the subject can continue in the study when recovered. The splenectomy is related to the automobile accident, not the product being studied. Therefore, no report is required.

Which of the following is NOT 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 a 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

D. Peer-reviewed scientific literature in support of the claim must be submitted in a preapproval supplement 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. (ii) In the case of an advertisement for a prescription drug other than a drug the labeling of which causes it to be an unapproved "new drug" and other than drugs covered by paragraph (e)(4)(i) of this section, an advertisement may recommend and suggest the drug only for those uses contained in the labeling thereof: (c) For which there exists substantial clinical experience (as used in this section this means substantial clinical experience adequately documented in medical literature or by other data (to be supplied to the Food and Drug Administration, if requested)), on the basis of which it can fairly and responsibly be concluded by qualified experts that the drug is safe and effective for such uses.

The following are required per 21 CFR Part 820 Quality System Regulation EXCEPT: A. Device History Record (DHR) B. Device Master Record (DMR) C. Design History File (DHF) D. Quality Manual (QM)

D. Quality Manual (QM) DHR is required per 21 CFR 820.184. DMR is required per 21 CFR 820.181. DHF is required per 21 CFR 820.30. Quality Manual is a requirement of ISO13485:2007. It is not required by QSR, although such a manual would be helpful in explaining the nature and extent of the QMS to an FDA investigator during an inspection.

A company is performing routine site monitoring of its pivotal clinical study for a blood sugar meter and finds one site has not properly consented one-third of its subjects. What is the FIRST thing the company needs to do? A. Stop the entire study B. Inform FDA and ask for guidance C. Re-train the study staff, including the principle investigator at that site on GCP D. Re-consent all improperly consented subjects

D. Re-consent all improperly consented subjects The improperly consented subjects must be properly consented immediately, and all study staff responsible for the conduct of the study need to be re-trained immediately after that. The company would also need to notify FDA to ask for guidance. The last measure should be to terminate the noncompliant site.

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 A Special Protocol Assessment applies to a Phase 3 study and has to be requested prior to initiating the study, so answer D 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 C A company is developing a new device, and the device classification under which it would fall is not clear. As the regulatory professional, you would make the following submission: is not applicable to this case, as Subpart H applies to utilization of surrogate, not well-established endpoints.

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

D. Submit a New Drug Application to CDER The primary mode of action determines the center to which a company should submit its application. Because the primary mode of action in this case is a drug, a new drug application should be submitted to CDER.

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

D. Submit an IND to start clinical safety trials in humans for approval of the product under 21 CFR 601 Subpart H. Because the target of the drug (the biothreat) causes irreversible morbidity or death, clinical efficacy studies in humans are not ethical. This eliminates choices A, B and C. However, approval under the Animal Rule (21 CFR 601 Subpart H) requires clinical safety data (to be completed in healthy volunteers).

A Special 510(k) must contain all of the following components EXCEPT: A. Proposed Labeling B. Design Controls Activity Summary C. 510(k) Summary or 510(k) Statement D. Summary of Safety and Effectiveness Data

D. Summary of Safety and Effectiveness Data Summary of Safety and Effectiveness Data is not a requirement of a Special 510(k). Sec. 807.87 Information required in a premarket notification submission. (j) For submissions claiming substantial equivalence to a device which has been classified into class III under section 513(b) of the act: (1) Which was introduced or delivered for introduction into interstate commerce for commercial distribution before December 1, 1990; and (2) For which no final regulation requiring premarket approval has been issued under section 515(b) of the act, a summary of the types of safety and effectiveness problems associated with the type of devices being compared and a citation to the information upon which the summary is based (class III summary). The 510(k) submitter shall also certify that a reasonable search of all information known or otherwise available about the class III device and other similar legally marketed devices has been conducted (class III certification), as described in 807.94. This information does not refer to information that already has been submitted to the Food and Drug Administration (FDA) under section 519 of the act. FDA may require the submission of the adverse safety and effectiveness data described in the class III summary or citation.

An Active Pharmaceutical Ingredient (API) manufacturer developed and validated a process to manufacture an active ingredient that is used in generic drug products. The API manufacturer is collaborating with three different generic manufacturers who are planning to submit an ANDA for another generic version of the drug. The API manufacturer submitted a Drug Master File (DMF) to FDA to describe the API's chemistry, manufacturing and controls. Which of the following is NOT true regarding the DMF? A. The API Manufacturer can authorize FDA to reference the DMF in the ANDAs of the three generic manufacturers B. Although the DMF is submitted to FDA, it is never approved or disapproved C. The API Manufacturer submits a Type II DMF for the active ingredient D. The API Manufacturer must update the DMF only when the submitted information changes or is no longer accurate

D. The API Manufacturer must update the DMF only when the submitted information changes or is no longer accurate "The holder should provide an annual report on the anniversary date of the original submission. This report should contain the required list ... and should also identify all changes and additional information incorporated into the DMF since the previous annual report on the subject matter of the DMF. If the subject matter of the DMF is unchanged, the DMF holder should provide a statement that the subject matter of the DMF is current. Failure to update or to assure FDA annually that previously submitted material and lists in the DMF remain current can cause delays in FDA review of a pending IND, NDA, ANDA, Export Application, or any amendment or supplement to such application; and FDA can initiate procedures for closure of the DMF (see Section IX)."

When design validation activities are being performed by a manufacturer, which element is NOT included as a requirement under the device design validation section of the QSR? A. Conformance to defined user needs and intended uses. B. Testing of production units under actual or simulated use conditions. C. Software validation and risk analysis, where appropriate. D. Translation of device design into production specifications.

D. Translation of device design into production specifications. Answers A-C are "design validation" activities. Answer 4 is an activity done under "design transfer." Design Transfer is outlined in 21 CFR 820.30(h) and relates to the establishment of procedures to ensure the device design is correctly translated into production specifications. Conformance to defined user needs and intended uses (answer A), testing under actual or simulated conditions (answer B) and software validation and risk analysis are all design validation activities.

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 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 previously-listed device, or when a previously-listed device is removed from commercial distribution.

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

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