Which of the following is NOT required for compliance under 21 CFR Part 11 (electronic records and electronic signatures)?
A Manually generated timestamped 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
C Authority checks to ensure that only authorized personell can create, modify or delete electronic records.
D Establishment of and adherence to written procedures
The final authority for ensuring the adequacy of an Investigational New Drug (IND) informed consent document resides with the:
Institutional Review Board (IRB)
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 that the labeling will be identical to that of the RLD. What process should be used to apply for that permission from FDA?
A 505(b)(2) NDA is not an appropriate regulatory submission for the approval to market a
New chemical entity when the sponsor has a right of reference to all applicable published studies
A mid-sized pharmaceutical company negotiated with FDA to submit a draft Package Insert (PI) and patient medication guide (MedGuide) 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?
Adverse event reporting for a marketed biologics product is NOT required for:
Diagnostic non-invasive test kits
The quality assurance manager of a small company consisting of 12 employees is the only internal auditor for the company 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
Auditor independence has not been ensured.
You have modified your 510(k)-cleared device with a Special 510(k). In which case would a Special 510(k) not be appropriate for the device?
You have changed the primary mechanism of action.
Which Premarket Approval Application (PMA) supplements are NOT subject to user fee exemption?
Real Time Supplement
A medical device company allows its sales force to maintain a product inventory in the field. The device has an expiration date indicated on its labeling. A sales person notes that one of his products has expired and contacts the headquarters office for direction. He is told to return the product to the headquarter office for replacement. The return of this product is considered as what type of recall?
Not a recall—it is considered normal stock rotation
A company is developing an (unapproved) drug-device combination product but is not sure to which center it should submit its marketing application. The company should first submit
A Request for Designation to the Office of Combination Products
A medical device company is developing a product with drug, biologic and device components. The product and indication have not been previously classified by FDA. What is the most appropriate regulatory pathway?
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 agency with primary jurisdiction.
FDA's Office of Generic Drugs (OGD) remains committed to the "first-in, first-reviewed" review order for the reviewing original Abbreviated New Drug Applications (ANDAs), amendments and supplements unless there is a specific reason to expedite an application. What is NOT a specific reason to grant expedited review?
Products that show evidence of safety and effectiveness in a new subpopulation
A firm is preparing a 510(k), premarket notification to FDA for an in vitro diagnostic test, a microhematocrit analyzer that, among other intended uses, can determine the hematocrit of a blood donor prior to donation of a blood product. The firm should address the 510(k) submission to:
Notice of Intent to Revoke license can be issued for the following reason, EXCEPT
A Unable to gain access to the manufacturing plant,
B Licensed product are no longer safe and effective
C Failure to report serious adverse event,
D Manufacturer fails to conform to applicable standards
What is the formal early collaboration meeting that was implemented through the Food and Drug Modernization Act (FDAMA)?
The Agreement Meeting is a formal meeting to agree upon 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. Regulatory Reference: Early Collaboration Meetings Under the FDA Modernization Act; Final Guidance for Industry and for CDRH Staff (February 2001).
A US medical device contract manufacturer has customers for whom it manufactures medical device components (parts) and finished medical devices. To date, all products have been either parts for Class II medical devices or Class II finished medical devices. The manager of new business contacts the regulatory manager to assess the impact of a possible new customer
involving a Class III device. What is the first question the regulatory manager should ask in order to begin assessing the impact of Class III on plant operations?
Is it a component or device that would be manufactured?
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 hum
You work for a company that is developing an autologous cellular therapy product. FDA has informed your company that your product will be regulated as a HCT/P (Human Cells, Tissues and Cellular and Tissue-Based Product). Based on this information, which of the following regulatory requirements will your company need to be compliant with when manufacturing
All Subparts of 21 CFR 1271 except Subpart C (Donor Eligibility)
A company has submitted its NDA for review. An NDA amendment can be submitted to change or add information to a not yet-
approved NDA. When must new safety information be submitted in a safety update report?
Four months after the initial NDA submission (120 day safety update)
A television advertisement that you have been asked to review prior to release discusses the benefits of the drug in detail for 25 seconds, and then names all the major side effects associated with the product in the last five seconds. You should advise that:
The benefits and side effects of the drug should be presented with the same level of scope, depth and detail.
At the completion of a Preapproval Inspection where a deficiency was noted, a meeting is convened to discuss what document?
Form FDA 483
Due to market interest, a new strength for an existing combination OTC product for use in the adult population (labeled as 12 years of age and older) has been developed, and appropriate data have been gathered to support safety and efficacy. The existing product is regulated by a final monograph, but does not contain labeling for use of the new strength in adult populations. What options could the company utilize to modify the monograph in order to gain FDA approval to market the new dosing regimen?
New Drug Application; Citizen's Petition; and Time and Extent Application
If a company is planning to market a medical device that is substantially equivalent to a device marketed before 1976, it can use which regulatory path?
If a device failure is occurring with greater than expected frequency and investigation of the problem indicates improper use by the end user, which of the following should occurs?
A The labeling is revised,
B The product is recalled,
C The product is redesigned,
D A Dear Doctor letter is issued
The labeling is revised
An Investigational New Drug Application (IND) goes to "Inactive Status" when:
No subjects are entered into clinical trials for a period of two years or IND is on clinical hold for one year.
Financial disclosure is required for investigators who, during the time the clinical investigator is carrying out the study and for one year following the completion of the study, have:
Been a prior employee of the sponsor company and own stock worth more than $50,000 (US)
An Investigational New Drug Application (IND) was submitted to FDA. New animal toxicology data is obtained and will be submitted to FDA as:
As an information amendment submitted no more than every 30 days.
Your company is planning to market an allergen patch test. Which center should oversee the approval process?
Your company wishes to seek approval of a combination of individually approved anti-hypertensive and anti-diabetic drugs.
However, there is no Reference Listed Drug for the proposed combination. Which regulatory pathways is most applicable?
Which of the following statements is TRUE for Phase 2 clinical investigations of a previously untested drug?
They are designed to determine the metabolic and pharmacokinect effects
B They are intended to gather additional info
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 bioavailability of the drug
They are conducted to determine the common short-term side effects and risks associated with the drug.
FDA has granted approval to market a product and has required a postmarketing commitment from the sponsor. The sponsor is required to gather additional information about the product's safety and use. Under what situations could FDA require the postmarketing study?
Approval granted in accordance with accelerated approval provisions, or the study is a deferred pediatric study under
All of the following choices are examples of type B meetings with FDA, except:
A PreIND meetings,
B Critical path meetings,
C End of Phase 2 meetings,
D PreNDA meeting
For a medical device's product storage and handling system, each manufacturer shall establish and maintain all of the following EXCEPT:
A Separate rooms or cages for release and quarantined material,
B Procedures for the control of storage areas and stock used for shipping supplies.,
C Environmentally controlled areas for product
D Procedures for rotation of stock.
Procedures for the control of storage areas and stock used for shipping supplies. There is no storage and handling requirement for shipping supplies.
A company's supplier of the active drug substance for the company's OTC monograph drug product informs the company that
the supplier 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?
The change does not have to be reported because it is an OTC monograph drug
Company Z selected a proprietary name for its new molecular entity currently in development. The New Drug Application (NDA) will be submitted in six months. All of the following are relevant to the proprietary name EXCEPT:
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.
A medical device company discovers that a surgeon participating as a clinical investigator in an IDE study sponsored by the company has independently placed a video demonstrating the use of the investigational device on YouTube.com. Should this action be considered as misbranding by the manufacturer?
No, as long as there the surgeon makes no claims related to safety or efficacy of the device
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 directly oversee the product manufactur
B Annual audits of operations.
C Document the dates and results of
D Have findings reviewed by management responsible for the product
Annual audits of operations.
FDA recommends periodic audits and does not specify a time. Regulatory Reference: 21 CFR 820.3(22)
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
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."
Which of the following is NOT stipulated by FDA to support product postapproval stability requirements?
A Three batches per year per containerclosure,
B An adequate number of batches.,
C An amount that is compliant with the postapproval stability commitments
D Reliable meaningful and specific test methods
Three batches per year per container/closure system in the stability program.
During the performance of a Class II product recall, additional complaint reports are received of the same product problem involved in the recall for products that were not in the date range of the lots being recalled. What action should the regulatory professional recommend to the company?
Reassess the root cause analysis, traceability data and rationale for the original recall range to determine why original assumptions were incorrect and notify FDA within 10 working days of the extended recall range.
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 Phase 3 protocol,
D Dose ranging protocol
A firm submitted and received approval for a clinical trial for IRB approval for a study involving children in which there would be no prospect of direct benefit to the individual subjects. On what basis could this study be approved by the IRB?
The trial was likely to yield generalized knowledge about the subject's disorder or condition and all other regulatory
requirements were met.
From a subsidiary in Ireland, you are forwarded a report that a patient taking your drug was hospitalized with a case of Stevens-Johnson syndrome. This hypersensitivity reaction is not listed on your label. You should report this case to FDA:
Within 15 calendar days of receipt
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 I studies,
B Phase II studies,
C Phase III studies,
D None of the above
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:
Compare the safety and effectiveness of the product for the claimed indications in pediatric and adult patients
A new Class II device with electrical components was subjected to extensive standard 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 manufacturer has the option to submit an Abbreviated 510(k) when FDA has recognized relevant consensus standards that are 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.
Per 21 CFR 820, a clinical study to establish safety and effectiveness of a device is considered:
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 equivalent to the product storage conditions.
D Any evidence of reserve sample deterioration should be reported
A reserve sample representative of one lot of shipped product per year must be retained.
All of the following would require a Type B Meeting request EXCEPT:
A Special Protocol Assessment SPA,
C End of Phase 2,
The Federal Trade Commission (FTC) has primary authority over which of the following?
A Overthecounter OTC drug advertising ,
B Prescription drug advertising,
C Generic drug advertising,
D Restricted edical device advertising
Overthecounter OTC drug advertising
Senior management at your company asked you to develop a justification for fast track status for an investigational new drug or epilepsy. Which of the following would be an appropriate justification for FDA granting fast track status for this
investigational new drug?
A preliminary evidence of effectiveness was seen in the principal controlled trials intended to provide evidence of effectiveness
B Epilepsy is considered by FDA to be a serious disease
C Pharmacokinetic profile of the new drug indicates less potential for toxic drug-drug interactions with other anticonvulsant
D Answers A B and C
Your company recently submitted a Biologics License Application (BLA) to CDER and the review division has notified you that you must develop and submit a Medication Guide. This request may have resulted from any of the following EXCEPT:
The product is one that has been demonstrated through adequate and well-controlled trials to be less effective than
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?
An Abbreviated 510(k)
When should the manufacturer of a Class III medical device expect to have an FDA establishment registration inspection?
Prior to approval of the PMA
During a periodic visit to a clinical investigator, the study monitor should assure all of the following EXCEPT:
A Informed consent has been documented in subjects
B The study protocol is being followed.
C The investigator has assigned activities in the protocol to other staff.
D Changes to the protocol have been approved
The investigator has assigned activities in the protocol to other staff.
A company is planning to develop a sunscreen with an ingredient consistent with its published monograph for marketing within the US. What type of filing does the company have to submit
At what timeframe after submitting an NDA will FDA provide the organization with an opportunity to meet with agency reviewing officials to inform applicants of the general progress and status of their application?
A medical device may be exported under Section 801(e) of the Food, Drug, and Cosmetic Act provided that all of the following apply for the device EXCEPT:
A It is in accordance with the specifications f the receiving country,
B It is not in conflict with the laws of the recieving country ,
C It is 510k cleared or PMA approved,
D It is labeled on the outside of the shipping carton for export to the receiving country.
It is 510(k) cleared or PMA approved
Which of the following is NOT true for an FDA inspection of a manufacturing facility?
A notice of inspection FDA 482 form is presented to the facility upon arrival,
B The credentials of the FDA investigator can be photocopied for filing at the facility.
C The FDA investigator provides inspectional report with the FDA 483 form,
D The FDA investigator provides an FDA 484 form to describe samples taken during the inspection.
The credentials of the FDA investigator can be photocopied for filing at the facility.
In order to be approved by FDA, a generic drug must be therapeutically equivalent to the branded product EXCEPT for:
A Dosage Form,
B Route of Administration,
C Inactive Ingredients,
A clinical investigator will conduct Phase I pharmacokinetic studies on your drug product. This same investigator also receives
a $30,000 retainer to be on the speaker's bureau for another of your company's products. What information related to this investigator must be included with your IND submission?
No additional forms are required.
Phase I pharmacokinetic studies are not covered studies, and therefore do not need financial certification or disclosure
The Quality System Regulation (QSR) provision for manufacturing reports on device manufacturing specifications by unit, lot
and batch is called the:
Device History Record
When design validation activities are being performed by a manufacturer, which element is NOT included as a requirement under device design validation section of the QSR?
A Conformance to defined user needs and intended use
B Testing of production units under actual or potential conditions
C Software validation.,
D Translation of device design into production specifications
Translation of device design into production specifications.
You receive an assignment to obtain a Special Protocol Assessment for a Phase 3 clinical trial of an investigational anti-TNF biologic for inflammatory bowel disease. You advise the clinical team and senior management as follows:
Submit a request to FDA for a Special Protocol Assessment as a separate IND amendment at least 90 days before the clinical trial is scheduled to begin.
90 days should be considered as the minimum time allowed between submission of the SPA and protocol start. Time must be
allowed to resolve issues. An SPA will not be awarded by FDA after a study has started.
Procedures for identifying the control number for each unit, lot or batch of finished devices is required for which type of medical device?
A Surgical gloves,
B Xray machines,
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 was not performed at enough sites
B The BLA was not submitted electronically
2 C The sponsor failed to have a meeting with FDA
D The submission did not include a Drug Master File
Clinical testing was not performed at enough testing sites.
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.
Which of the following is NOT required in a Biologics License Application (BLA) but is required in an New Drug Application
A FDA form 3397 user fee cover sheet,
B Field copy certification,
C Chemistry section,
D Patent certification
Field copy certification,
Field copy certification only applies to NDA products
An applicant is required to submit patent information when approval is sought in which of the following supplements submitted
to an approved marketing application?
A Change in the formulation,
B Change in manufacturing site,
C Change in the sponsor,
D Change in the formulation and in the manufanufacturing site
Change in the formulation
An applicant is required to submit patent information when approval is sought in supplements involving a formulation change, a new condition of use, a new indication, a change in the route of administration, a change in strength or any other patented change regarding the drug, drug product, or method of use.
While reviewing the data for an upcoming New Drug Application (NDA) submission, the in-house monitor found that the investigator's Curriculum Vitae (CV) had not been updated throughout an Investigational New Drug (IND) Study. According to FDA guidance on Form FDA 1572, how often should the investigator's CV be updated?
It does not need to be updated
A US medical device company wants to sell a Class III product in Australia, where it has recently obtained approval. However, this product does not currently have approval in the US. The product is manufactured in accordance with the US Quality Systems Regulations. Which is the appropriate regulatory action in the US before the product can be exported to Australia?
Send Simple Notification to FDA and obtain an 802 Certificate of Exportability from FDA (if requested by Australia).
All of the following are types of regulatory inspections for a pharmaceutical product EXCEPT?
A PAI, B For cause, C QSR, D GMP
QSR audits are performed for medical devices
Which of the following is considered part of the Device Master Record?
A Employee training record,
B Serial number label,
C Design reviews,
D Calibration records
Serial number label
While seeking a new Class III indication for a medical device that is currently on the market as Class II, a company received a vote of "non-approvable" from an FDA Advisory Panel. Possible courses of action include all of the following EXCEPT:
A Continue marketing the device for its Class,
B Update the current labeling to include the new indication,
C Proceed with a PMA submission to FDA.,
D Request a facetoface postpanel meeting with the FDA
Update the current labeling to include the new indication,
Which of the following statements is NOT true with respect to both Investigational New Drug (IND) Applications and Investigational Device Exemptions (IDEs) for significant-risk products?
A The investigational product must be manufactured in full compliance with CGMP.
B Clinical studies must be reviewed and approved by an IRB,
C The IND or IDE goes into effect 30 days after submission if no response is recieved from the FDA
D The application must include an environment risk assesment or a categorical exclusion for not providing one.
The investigational product must be manufactured in full compliance with CGMP.
Devices under approved IDEs are exempt from CGMP regulations except for design control requirements; investigational new drugs must be compliant with CGMP for finished pharmaceuticals.
FDA currently requires that all medical device registration and listing information (Annual, Initial or Updates) be submitted using:
A FDAs Unified Registration and Listing System
B FDA Forms 2891 and 2892,
C FDA Forms 2656 and 2657,
D FDA Form 3356
FDAs Unified Registration and Listing System
What type of communication will FDA send to 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?
Complete response letter
A firm received a raw material for one of its drug products. The raw material was placed into quarantine and sampled appropriately. Sample containers should be identified so that the following information can be determined
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.
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
B Device Y is approved for marketing in the US
C Warning Device Y is not compatible with MRI use
D Caution Device Y when improperly deployed can cause bleeding
Device Y is approved for marketing in the US.
Class II devices are cleared for marketing in the US by the FDA, not approved.
The manufacturer of a drug is closing the currently approved manufacturing facility for the approved drug product. The current
facility has old equipment and has suffered product contamination issues and poor quality in the past 12 months. The manufacturer has two other facilities that can accommodate the existing manufacturing process. The company president
asked regulatory to examine the two locations and to develop an appropriate regulatory strategy. Facility A is a large facility being built near the facility being closed. It will have state of the art electronics to monitor the manufacturing process, all new isolated manufacturing areas, and all new equipment. This new facility will be open one month before the other facility is
scheduled to close. This manufacturing process will be the first process moved to this new building. Facility B is a smaller facility that is 100 miles away from the facility being closed. This 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?
Facility B is already 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
When FDA declares a device from a 510(k) application to be Not Substantially Equivalent (NSE) and requires a PMA. What is the most practicable first option for a company at this stage?
A File a PMA immediately.,
B Petition CDRH to downclassify the device using de novo reclassification
C Resubmit a 510(k) with new data to demonstrate the device is at least as safe and effective as the predicate.
D Submit this product for approval in Europe
Resubmit a 510(k) with new data to demonstrate the device is at least as safe and effective as the predicate.
Although an NSE Letter places the devices into the PMA category, FDA allows a company to refile the 510(k) with new data to demonstrate the device is at least as safe
and effective as the predicate. Petition to down-classify the device is the option when there are no comparable predicate devices but the "most practical" option is to refile
the 510(k). The other goal of this question is to inform the examinee that although an NSE Letter places the device into the PMA category, it does not mean FDA is asking
for a PMA filing.
Which of the following is NOT an example of an annual reportable change for a marketed product?
A Deletion of a specification for drug substance
B A change in specification made to comply with a pharmacopeia
C An editorial change to a label.,
D Tightening of acceptance criteria.
Deletion of a specification for drug substance.
The two mechanisms to amend an OTC Monograph are:
Time & Extent Application (TEA) or Citizen Petition
A company is using a clinical research organization (CRO) to develop the protocol and monitor the clinical investigators for its
clinical trial. The regulatory professional may interact with the CRO in which of the following situations?
A Making presentations to the reviewing IRBs.
B Making presentations to the reviewing division
C Witnessing the signing of patient consent forms
D Arranging for FDA investigators to observe treatment of subjects at clinical sites
Making presentations to the reviewing division at FDA.
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
Present three years of real time stability data on three consecutive batches in the NDA Annual Report.
During a review of the production records for Batch 1 of Drug Product X, it was discovered that the theoretical yield exceeded the maximum percentage established in the master production and control records by 1.5 percent. The batch has not been distributed. As a regulatory professional, you should recommend that the investigation:
Be extended to other drug products that may have been associated with the discrepancy
Your company will now utilize alternate suppliers for the compendial ingredients of an NDA product. How should this change be reported?
CDER need not be notified of this type of change.
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 for these batches 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?
Actual yield and percentage of theoretical yield
Phase 2 clinical trials are being planned for a novel cancer drug. All of the following are appropriate factors in this phase of the
A 150 cancer patients,
B 150 healthy subjects,
C One or more indications,
D One or more dose regimens
150 healthy subjects,
A company begins to market its new device, a pacemaker (Class III) the same day that its regulatory professional mails the Premarket Approval Application (PMA) to FDA. The pacemaker is considered: