2014 Practice RAC Exam – Flashcards

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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)."

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.

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.

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.

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.

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.

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.

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.

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.

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.

A. The product is regulated as a drug Primary mode of action is the pain drug and the device is a delivery system.

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)).

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.

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.

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.

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).

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.

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.

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. 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)).

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.

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.

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.

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.

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.

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.

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

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.

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).

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

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.

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.

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.

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.

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.

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.

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).

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.

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 the communicable disease agents for which testing is required under paragraphs (a) and (b) of this section, as applicable, and except as provided under 1271.90, you must test a specimen from the donor of reproductive cells or tissue to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents of the genitourinary tract. Such testing must include testing for the communicable disease agents listed in paragraphs (c)(1) and (c)(2) of this section. However, if the reproductive cells or tissues are recovered by a method that ensures freedom from contamination of the cells or tissue by infectious disease organisms that may be present in the genitourinary tract, then testing for the communicable disease agents listed in paragraphs (c)(1) and (c)(2) of this section is not required. Communicable disease agents of the genitourinary tract for which you must test include: (1) Chlamydia trachomatis; and (2) Neisseria gonorrhea.

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.

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.

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.

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.

B. Device Y is approved for marketing in the US. Class II devices are cleared for marketing in the US by FDA, not approved.

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

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.

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."

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.

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 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. To avoid unnecessary duplication in the submission to FDA of reports required by paragraphs (c)(1)(i) and (c)(1)(ii) of this section, obligations of a nonapplicant may be met by submission of all reports of serious adverse drug experiences to the applicant. If a nonapplicant elects to submit adverse drug experience reports to the applicant rather than to FDA, the nonapplicant shall submit each report to the applicant within 5 calendar days of receipt of the report by the nonapplicant, and the applicant shall then comply with the requirements of this section.

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.

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.

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.

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.

A. Compliance Branch in the appropriate FDA District office This office is the best source for further follow up.

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. 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.

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.

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

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."

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.

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.

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. 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. 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.

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."

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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"

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.

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.

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. 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. 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.

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.

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.

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.

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 4 is correct. Fast Track designation can be requested at any time. Priority review is requested prior to filing an NDA, not prior to clinical studies. Answer 3 is not applicable to this case, as Subpart H applies to utilization of surrogate, not well-established endpoints.

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 3.

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

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

B. Process validation protocols and reports Process validation protocols and reports are not required to be submitted as part of the RFD.

A. This complaint is reportable; an MDR will be filed with FDA within 30 days When a recall is initiated for a particular product failure mode, such failure mode is automatically MDR-reportable to FDA. Additionally, while the complaint did not report an adverse event, the manufacturer should evaluate the potential to cause an adverse event if the failure mode was to re-occur.

C. IDE 5-day Notice IND Supplements and CBE-30 submissions are for drugs. A PMA amendment includes all additional submissions to a PMA or PMA supplement before approval of the PMA or PMA supplement or all additional correspondence after PMA or PMA supplement approval. During the conduct of a clinical study for a device, if minor manufacturing changes are made, these changes can be reported to FDA in an IDE 5-Day Notice.

B. The proprietary name submission package may be submitted up to one month after NDA submission. The request for proprietary name approval must be submitted no later than in the NDA. Companies have the option of submitting a proprietary name request prior to NDA submission under the Investigational New Drug application (IND). FDA review of proprietary names evaluates both the proposed names' safety and promotional aspects. FDA will inform the applicant prior to the action date whether the proprietary name is acceptable and will offer suggestions if the proposed name is deemed unacceptable. Sec. 314.50 Content and format of an application. (a)Application form. The applicant shall submit a completed and signed application form that contains the following: (1) The name and address of the applicant; the date of the application; the application number if previously issued (for example, if the application is a resubmission, an amendment, or a supplement); the name of the drug product, including its established, proprietary, code, and chemical names;

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

D. New Chemical Entity when the sponsor has a right of reference to all applicable published studies A 505(b)2 NDA is an application where approval of the new drug relies on data at least in part that is not developed by the applicant. 505(b)(2) Application means an application submitted under section 505(b)(1) of the act for a drug for which the investigations described in section 505(b)(1)(A) of the act and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.

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).

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

A. The product is regulated as a drug Primary mode of action is the pain drug and the device is a delivery system.

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

D. Design validation The clinical study is objective evidence the device specifications conform with the user needs and intended use.

D. Carcinogenicity Carcinogenicity is required to demonstrate long-term safety of an implant. All other testing is required for acute safety.

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

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.

C. The subjects are satisfied with the treatment they receive

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.

C. An application requesting federal exemption from interstate commerce law The IND is not a request for approval; it is a request for exemption from federal law governing the movement of unapproved products across state lines.

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

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 1, 2 and 3. However, approval under the Animal Rule (21 CFR 601 Subpart H) requires clinical safety data (to be completed in healthy volunteers).

A. A new 510k needs to be submitted with an appropriate testing for the new indication A new indication for use requires a new 510(k) clearance.

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.

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

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

D. Facility B has been manufacturing approved drug products for the same therapeutic purpose for the past 15 years and has been inspected by FDA. The move of the manufacturing process to Facility B would be a moderate change and could be filed in a CBE 30. The transfer of a drug product manufacturing process to a new facility requires notification of FDA of the change to the process. In reviewing Facilities A and B, the regulatory professional would recognize that Facility A, although new and state-of-the-art, has not been inspected by FDA and would result in a major change to the approved NDA. This major change would require a prior approval before drug product manufactured in this location could be placed onto the market. Reporting of this manufacturing change in an Annual Report would be incorrect. The transfer of the manufacturing process to Facility B, however, would be a moderate change as FDA has inspected it for the other drug products it currently manufactures. This is considered a moderate change and would result in a Changes Being Effected (CBE) 30 notification to FDA prior to placing the drug product manufactured on the market.

A. Clearly identify what the inspector was requesting and thoroughly review all documentation before presenting the documentation to the inspector An FDA inspector can request and receive the audit schedule information to establish the company has an internal audit program. However, a company is not obligated to provide internal audit report summaries. In this case, the internal audit summary was provided by the company in error, not at the request of the inspector. It is important for a company to provide only information that is requested by an inspector. The inspector can use any information provided to him or her to identify deficiencies in a company's Quality System, even if it was not requested. Sec. 820.22 Quality audit. Each manufacturer shall establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. Quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited. Corrective action(s), including a re-audit of deficient matters, shall be taken when necessary. A report of the results of each quality audit, and re-audit(s) where taken, shall be made and such reports shall be reviewed by management having responsibility for the matters audited. The dates and results of quality audits and reaudits shall be documented. Guidance: Under the law, your firm is responsible for conducting internal self-audits to identify and correct any and all violations of the quality system requirements.

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.

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.

C. Mandatory for manufacturers but voluntary for healthcare professionals. "(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 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. To avoid unnecessary duplication in the submission to FDA of reports required by paragraphs (c)(1)(i) and (c)(1)(ii) of this section, obligations of a nonapplicant may be met by submission of all reports of serious adverse drug experiences to the applicant. If a nonapplicant elects to submit adverse drug experience reports to the applicant rather than to FDA, the nonapplicant shall submit each report to the applicant within 5 calendar days of receipt of the report by the nonapplicant, and the applicant shall then comply with the requirements of this section.

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.

B. Special PMA Supplement—Changes Being Effected The Special PMA Supplement is used when the change enhances or increases the device's safety.

C. Report to FDA in Form 3500A (MDR) within 30 days of becoming aware of the event Under FD&C Act Section 503(g) (1), assignment to lead center is based upon the combination product's primary mode of action (PMOA). In this product, the device has the PMOA. As a device it follows the MDR reporting requirements. Answers A and B are postmarket reporting requirements for drugs. Answer C is a reporting requirement for medical devices, 30-day reporting timeframe for serious adverse consequence. Answer 4 is an IND reporting requirement. Therefore, 3 is the correct answer.

C. Within 75 days of the agency's receipt of the meeting request. Type C meetings should be scheduled to occur within 75 days of the agency's receipt of the written request for a meeting.

B. Contracting with another manufacturer that would manufacture the product under your license Answer B is the ideal choice as it would represent the least disruption to both your facility and the product labeling since the contractor would be operating under your license. Your license must be amended to include the contract manufacturer and quality/regulatory oversight must be maintained through the quality agreement/contract with the contractor. Under the scenarios in answers A and C, your labeling will have to indicate the new manufacturer. Answer D is not appropriate since short supply agreements are to be used only in specific circumstances not part of this scenario.

C. Product recall Market withdrawal is not subject to legal action by FDA. (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 (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.

C. 6 Months Manufacturers shall retain for a period of at least six months after the expiration date, unless a different time period is specified in additional standards, a quantity of representative material of each lot of each product, sufficient for examination and testing for safety and potency, except Whole Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, and Source Plasma and Allergenic Products prepared to a physician's prescription.

C. Major or minor deficiencies are identified with the clinical data after substantive review by FDA Substantive review of the PMA submission will begin once FDA determines the submission will not be refused.

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

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.

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

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.

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.

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