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U.S. Department of Health and Human Services

Medical Devices

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Inspection of Medical Device Manufacturers: Part III Inspectional

PART III

INSPECTIONAL

BACKGROUND

This program includes guidance for determining compliance with the Quality System (QS) regulation, Medical Device Reporting (MDR) regulation, Medical Device Tracking regulation, Corrections and Removals regulation, and the Registration and Listing regulation.

A. OPERATIONS

1. Inspectional Strategy

The QS inspectional goal is to assess the firm’s quality management system for compliance with the appropriate regulations.  The QS inspection should generally start with a walk through of the facility to become familiar with the firm’s operations and general state of control.  See IOM 5.1.2.2.

The inspection will assess the firm’s systems, methods, and procedures to ensure that the firm’s quality management system is effectively established (defined, documented and implemented) and effectively maintained.  QS inspections should include the assessment of post-market information on distributed devices to include:

  • Review of recalls
  • Review of MDRs (Be alert to the fact that MDRs may contain information on recalls that have not been reported through the district under 21 CFR Part 806.)
  • Review of corrections and removals
  • Review of significant changes in device specifications or in the manufacturing specifications
  • Follow-up on previous FDA 483 observation(s), to include the corrections, corrective actions or preventive actions for the observation(s) and the related system(s

Available post-market information should be reviewed as a part of the preparation for the inspection, in order to facilitate efficient time spent at the facility.  Identify in the EIR post-market information reviewed during the inspection, and adequately document your findings.  See IOM 5.10.4.3.9.  Any problems identified as a result of the review of post-market information should be developed during the inspection.

Important Note:  The review of post-market information does not mean that the investigator should open the inspection with the review of complaints and complaint information. Complaints should be reviewed within the context of the Corrective and Preventive Action sub-system according to the procedures described below in this part.

a. QS Inspections

QS inspections should generally be conducted using the Quality System Inspection Technique (QSIT).   Guidance for performing an inspection is provided in the Guide to Inspections of Quality Systems, August 1999, also called the QSIT Guide [http://www.fda.gov/downloads/ICECI/Inspections/UCM142981.pdf].  This QSIT tool can be scaled to meet the needs of each particular inspection.  The table below correlates the level of inspection and the guidance on how to perform the inspections.

                                 

TABLE

Inspection
Level

Type of Inspection

Guide to Inspections

1

Abbreviated

QSIT – Two subsystems; Corrective and Preventive Actions (CAPA) plus Production and Process Controls (P&PC) or Design Controls
(PAC 82845A)

2

Comprehensive

QSIT - The four major subsystems; Management Controls, Design Controls, CAPA and P&PC
(PAC 82845B or 82845P or 82A800)

3

Compliance Follow-up*

 

As directed by inspectional guidance and elements of QSIT
(PAC 82845C)

Special

For Cause*

As directed by inspectional guidance and elements of QSIT
(PAC 82845G)

Special

Risk Based Work Plan

As directed by CDRH inspection assignment and elements of QSIT
(PAC 82845H)

*Compliance Follow-up, For Cause, and Risk Based Work Plan inspections are dictated by the previous FDA 483 findings and other regulatory information and may differ from the typical QSIT approach.  The inspectional guidance provided by the assignment, the district compliance branch, and/or CDRH will guide the direction of these inspections.  However, elements of the QSIT Guide may also be utilized.  See further details below.  Investigators must ensure that the EIR clearly states what was covered during the inspection due to the directed nature of these types of inspections.

NOTE:  The Quality System regulation can be grouped into seven subsystems; however, the following four subsystems are considered major subsystems and are the basic foundation of a firm’s quality management system: Management Controls, Design Controls, Corrective and Preventive Actions (CAPA), and Production and Process Controls (P&PC).  MDR, Corrections and Removals, and Tracking requirements (where applicable) should be covered when covering the CAPA subsystem.  The three remaining subsystems (Facilities and Equipment Controls, Materials Controls and Document/Records/Change Controls) cut across a firm’s quality management system and are evaluated while covering the four major subsystems.

In the work plan, Level 1 Abbreviated (82845A), Level 2 Comprehensive (82845B), Level 3 Compliance Follow-Up (82845C), For Cause (82845G), Risk Based Work Plan (82845H) and Accredited Persons (82845P or 82A800) inspections are planned for each district.  Planning resources for these five PACs provides greater control at the district level on the type of inspection conducted to maximize resource utilization and provide the flexibility needed to insure the Performance Goals are met.  In utilizing this flexibility, districts must continue to monitor their accomplishments to assure that the Performance Goals and work plan are met.

b. Level 1 Inspections - PAC 82845A

Level 1 inspections are Abbreviated Inspections. 

This level of inspection (CAPA plus P&PC or Design Controls) may be used for routine surveillance and initial inspections of all firms, other than firms that manufacture Class III devices.  However, it is recommended that initial inspections of Class II manufacturers utilize a Level 2 Comprehensive inspection whenever district resources permit.  Level 1 inspections should cover the CAPA subsystem, then P&PC or Design Controls, using the QSIT Guide.  The selection of CAPA plus either the P&PC or Design Controls subsystem will provide an adequate review of the compliance status of the firm.

The following should be considered in determining whether to select P&PC or Design Controls:

  • CAPA findings during the inspection
  • Subsystems covered during the previous EI. The previous EIR(s) should be reviewed to determine which subsystems were previously covered.  The selection of the P&PC or Design Controls subsystem should be alternated over time so that more subsystems within a firm’s overall quality management system are assessed
  • Significant changes since the previous EI. Determine if there were any design changes which required a new submission or application, or if there were any major process changes
  • Post market information indicating potential design problems.

The EIR must clearly state which subsystem, P&PC or Design Controls, was chosen and why.

Note:  The adequacy of the correction(s), corrective action(s) or preventive action(s) related to any FDA 483 item(s) from the previous inspection should be covered, even if the entire subsystem will not be reviewed during the current Level 1 inspection.

c. Level 2 Inspections - PAC 82845B or 82845P

Level 2 inspections are Comprehensive Inspections. 

Level 2 inspections will cover all four major subsystems (Management Controls, Design Controls, CAPA, and P&PC) as explained in the QSIT Guide.  The Level 2 inspection is considered a comprehensive review of the compliance status of the firm. 

Level 2 inspections will be performed:

  • For all initial inspections of Class III device manufacturers and, where possible, Class II device manufacturers
  • By assignment
  • For foreign inspections
  • For training
  • For Accredited Persons audits (PAC 82845P)
  • When an inspection, which started out as Level 1, reveals post market information and/or objectionable conditions which cannot be adequately assessed as a Level 1 inspection.  (Before converting to this more comprehensive level, district management should be informed.)
  • Where district work plan resources permit (Level 2 should be considered for any inspections of Class II and Class III device manufacturers.  The decision to use Level 2 inspections should be based on risk.)

Note:  For more information on the Accredited Person audits see “Accredited Person Inspection Program (Medical Devices) Performance Audit Procedures” on the Division of Human Resource Development’s (DHRD’s) intranet website under the certification/related programs/accredited person program section.

The Level 2 QSIT approach was validated using the following inspectional sequence:  Management Controls, Design Controls, CAPA and P&PC.  This inspectional sequence allows the investigator to review design control issues and how the device specifications were established before reviewing the CAPA subsystem.  Investigators may, however, start with Management Controls, followed by CAPA, Design Controls, and P&PC with appropriate linkages.   Information from Design Controls and CAPA may be used to select the products and processes for inspecting production and process controls, and appropriate linkages.   The subsystems may be inspected in any appropriate and justifiable sequence in order to perform a timely and effective inspection.

Selection of manufacturing processes for inspectional coverage should include the following considerations:

  • CAPA indicators of process problems
  • Processes used to manufacture high risk products
  • Processes that have a high risk of causing product failure
  • Processes that require process validation
  • Processes that are new to the manufacturer
  • Processes that cover a variety of process technologies and profile classes
  • Common processes used in multiple products
  • Processes not covered during previous inspections

It is important to thoroughly cover Purchasing Controls, to include outsourced processes, as a QSIT linkage under P&PC whenever P & PC is covered.  The Purchasing Control coverage must be documented in the EIR, especially if the manufacturer contracts a sterilization process or contracts the manufacture of significant components, subassemblies, or processes.

d. Level 3 Inspections - PAC 82845C

Level 3 inspections are Compliance Follow-up Inspections.

Level 3 inspections are necessary after a firm is found to have Situation I conditions during a previous QS inspection which was classified Official Action Indicated (OAI).  (See Part V of this compliance program for information on Situation I and OAI.)   Level 3 inspections will also be performed when directed by assignment.

The QSIT Guide should be used for guidance, but the inspectional guidance provided by the assignment, the district compliance branch, and/or CDRH will guide the flow of the inspection. The district compliance officers should be contacted during Level 3 inspections to assure that:

  • Appropriate inspectional areas are covered with enough depth to support any findings
  • Noncompliant findings (conditions) are adequately developed and documented
  • Sufficient evidence is collected to support an appropriate regulatory action recommendation

Note:  Foreign inspections, as discussed below, are Level 2 inspections and, therefore, the option to stop an inspection in the next two diagrams does not apply.

If the previous inspection was a Level 2 inspection:         

During domestic Level 3 inspections: 

(A) Verify that adequate correction(s) and corrective action(s) have been implemented to the quality system problems previously identified.

(B) If the correction(s) and corrective action(s) were not implemented or were not implemented effectively, verify that the deficiencies continue to exist and provide adequate evidence to support a possible regulatory action. 

(C) Document any additional quality system problems observed during the inspection, and provide adequate evidence to support a possible regulatory action.

The chart below describes the steps for the Level 3 domestic inspection after a Level 2 inspection.

***********CHART

If the previous inspection was a Level 1 inspection: 

When the previous inspection was performed as a Level 1 inspection, the other two major subsystems previously not covered must be covered in addition to the inspectional guidance. It is important that the combination of the Level 1 and Level 3 inspections cover all four of the major subsystems in order to ensure a comprehensive review of the firm’s quality management system.

During domestic Level 3 inspections:

(A) Verify that adequate correction(s) and corrective action(s) have been implemented to the quality system problems previously identified; and

(B) If the correction(s) and corrective action(s) were not implemented or were not implemented effectively, verify that the deficiencies continue to exist and provide adequate evidence to support a possible regulatory action. 

(C) Document any additional quality system problems observed during the inspection, and provide adequate evidence to support a possible regulatory action. 

The chart below describes the steps for the Level 3 domestic inspection after a Level 1 inspection.

***********CHART

e. For Cause Inspections - PAC 82845G

For Cause inspections are carried out in response to specific information that raises questions, concerns, or problems associated with a FDA regulated firm or commodity. This information could come to the attention of FDA from any source and including, but not limited to, the following:

  • Results of a sample analysis
  • Observations made during prior inspections
  • Recall or market withdrawal
  • Consumer or employee complaint
  • Adverse reaction report
  • Suspicion of fraud

For Cause inspections are usually initiated at the request of CDRH, ORA headquarters, Regional or District directives.   For Cause inspections are dictated by the source of information and may differ from the typical QSIT approach.  These inspections are generally more in-depth in particular areas than typical QSIT inspections.  The inspectional guidance provided by the assignment, the district compliance branch, and/or CDRH will guide the flow of these inspections, however, elements of the QSIT Guide may also be utilized.

For Cause inspections should be directed towards the quality problem(s) and, if applicable, trace the underlying cause, assuring that appropriate correction(s) and corrective action(s) are initiated. 

If a serious public health risk is encountered during a QSIT inspection, consideration should be given to performing a For Cause inspection.  The district compliance branch should be consulted prior to this decision. 

For Cause inspections may also be initiated at a contract sterilizer when an inspection at a device manufacturer raises questions about the adequacy of processing or quality assurance by the contract sterilizer.  Likewise, an inspection at a contract sterilizer may lead to a For Cause inspection of device manufacturers if significant deficiencies are observed.  The deficiencies may be an indication that the device manufacturer(s) has not assumed appropriate responsibility for the sterilization validation and processing of its own devices.  The district that has identified the need for the additional coverage is to notify the home district of the establishment that needs a For Cause inspection.

f. Risk Based Work Plan Inspections - PAC 82845H

The risk based work plan inspection program was developed to focus limited resources on key public health needs.  It reflects the broader goals of the Center and Agency to utilize science-based risk management in the selection and prioritization of sites for inspection. This provides the most health promotion and protection to the public at the least cost by focusing on medical devices and firms which pose the greatest risk. 

Data collected throughout the total product life cycle (e.g. premarket submissions, recalls, adverse event reports) is analyzed to detect risks posed by medical devices.  The beneficial public health impact of the devices and the potential risks of device failure are also considered.  In general, the project’s objectives include the following:

  • a more consistent, rigorous, science-based approach to selection of sites for inspection
  • increased transparency and rigor in decision making
  • employment of limited resources towards sites that pose the potentially greatest risk to public health

Risk based work plan inspections are initiated at the request of CDRH.  These inspections are focused by the Center’s analysis and work plan assignment and may differ from the typical QSIT approach.  These inspections are generally more in-depth in particular areas than typical QSIT inspections.  The inspectional guidance provided by the assignment will guide the flow of these inspections; however, elements of the QSIT Guide may also be utilized.

If a serious public health risk is encountered during a risk based work plan inspection, CDRH and the district compliance branch should be consulted.  

g. Foreign Inspections

All foreign inspections should be conducted using the QSIT Guide under the Level 2 strategy, and any special instructions contained in the inspection assignment.  The foreign manufacturer's compliance with registration and listing requirements should be covered during foreign inspections.  The failure of foreign device manufacturers to list products exported to the US will subject medical devices to detention upon entry.

Foreign inspections are subject to time constraints but need to follow the instructions for a Level 2 inspection as described above.  Requests for documents should be made as early as possible to give the firm time for written or oral translations and obtaining documents that may be located in US offices.  Oral translations need to be documented in the EIR if that information is utilized in supporting an observation(s).

2. Inspectional Instructions

a. Required Statement(s)

The following statement should be included on each FDA 483: 

This document lists observations made by the FDA representative(s) during the inspection of your facility.  They are inspectional observations and do not represent a final Agency determination regarding your compliance.  If you have an objection regarding an observation, or have implemented, or plan to implement, corrective actions in response to an observation, you may discuss the objection or action with FDA representative(s) during the inspection or submit this information to FDA at the address above.  If you have any questions, please contact FDA at the phone number and address above.

For all medical device inspections the FDA 483 should contain the following additional statement: 

The observations noted in this form FDA 483 are not an exhaustive listing of objectionable conditions.  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.
 

b. Satellite Program Areas

Some program areas are considered satellites to the four major quality management system subsystems (Management Controls, Design Controls, CAPA, and P&PC):

CAPA Satellites:

  • MDR
  • Corrections & Removals
  • Tracking

Production & Process Control Satellite

  • Sterilization

Refer to the QSIT Guide for details on how to inspect those areas mentioned above. Refer to Part V of this Compliance Program for guidance on Regulatory and Administrative follow-up to these programs.  Report the time spent on the Satellites under the appropriate corresponding PAC.  Time for coverage of these satellites is averaged into the Level 1 and Level 2 inspectional work plan modules.

The following guidance should be used for determining when to cover the various programs.

QS should be covered during each inspection.   Coverage is determined by the "level" of desired inspection.  See Part III, above for guidance on which level to use and which subsystems to inspect.

MDR compliance should be covered during each inspection.  Prior to initiating an inspection, the MDR data should be reviewed using eCIRS or by going to CDRH to obtain information regarding the firm’s current reports.  Be alert to the fact that MDRs may contain information on recalls that have not been reported through the district under 21 CFR Part 806.

Corrections & Removals.  Determine during all QS inspections whether the firm has initiated any corrections or removals since the previous inspection, and inspect for compliance with the Corrections & Removals regulation as described in the QSIT Guide. A Corrections & Removals inspection should also be initiated when a manufacturer is reporting corrections or removals in MDR reports or Part 806 reports.  Be alert to the fact that MDRs may contain information on recalls that have not been reported through the district under 21 CFR Part 806.

Tracking.  A tracking inspection is recommended for devices that were issued a tracking order, each time CAPA is covered.  To obtain Tracking information, refer to “Medical Device Tracking Guidance for Industry and FDA Staff” dated May 5, 2003, or access http://www.fda.gov/cdrh/comp/guidance/169.html.

Sterilization.  When the P & PC subsystem is being inspected, sterilization should be chosen if not covered during the previous inspection unless:

  • CAPA indicators of existing or potential problems are found with any other specific process or,
  • Other higher risk processes exist.

c.  Sampling Records

The QSIT Guide includes instructions for sampling records for review.  Sampling is an important tool for reducing the time spent reviewing records while being able to make statistically based inferences about the significance of the findings.  The QSIT sampling table should be used for sampling records for evaluating the firm’s adherence to requirements and their procedures, not for performing data verification or analysis.

During Level 1 and 2 inspections, the review of the records may be terminated if objectionable conditions are observed before the entire sample is reviewed.  An FDA 483 observation may be made that the objectionable condition was found, and then move to the next part of the inspection.  However, QSIT Guide instructions caution that not reviewing the entire sample may result in the loss of additional information which may be useful in understanding the potential prevalence of the objectionable condition, or the failure to identify other objectionable conditions. 

During Level 3 inspections, however, the investigator and the compliance officer should work together closely to plan how sampling will be conducted.  It is important for the compliance officer to be confident that the level of sampling will be sufficient to document the deficiency and support a potential regulatory action.  During Level 3 inspections, it is recommended that the investigator review the entire sample of records to provide a complete picture of any deficiencies identified during sampling.

When evidence is collected utilizing the sampling tables, the EIR should reflect the following information:

  • The type of records reviewed
  • The sampling table used, Table 1 or 2
  • The row used, row A, B, C, D, E or F
  • The size of the sample and the number of records it was based on 
  • The number of records actually reviewed (may be the same as or different from the size of the sample)
  • The results of sample review

Computer aided techniques may also be useful tools to efficiently evaluate electronic records (e.g. a large volume of complaint files) or accomplish assignment specific objectives (e.g., evaluating for trends in product specific complaint or failure data). 

Note:  Statistical support is available from CDRH, Office of Surveillance and Biometrics. DFI experts are available to assist with support in applying computer aided techniques.

3. Special Instructions Concerning Design Controls

The inspectional authority for review of design control records is derived from Section 704(e) of the Act.  Such authority applies only after the establishment has manufactured the device for which the design has been under development or taken an action that precludes the argument that the product under development is not a device.  Such action includes:  (1) submitting to an Institutional Review Board plans for clinical investigation of the device, (2) submitting to FDA a Product Development Protocol (PDP), (3) submitting to FDA an IDE, 510(k), PMA, Humanitarian Device Exemption (HDE) or Premarket Report (PMR), and (4) changes to an already marketed device.  Therefore, FDA has inspectional authority to review design control records when the device has been placed on the market or when any of the four actions above have occurred.

The above limitation does not apply to inspectional authority to review all generic design control procedures at any point in time.

Review of design controls should cover any design processes performed after June 1, 1997.  The manufacturer is not required to retrospectively apply design controls to any stages in the design process that it had completed prior to June 1, 1997, unless changes have been made to the design (including changes in ownership or where the designed device will be manufactured) after June 1, 1997.

If a manufacturer normally designs its own devices, but has not initiated any design changes to current devices since June 1, 1997, or does not have a design project underway that is reviewable by FDA given the limitation discussed above, investigators should limit their coverage to a review of the design change control procedures that the manufacturer must have defined and documented.

There are a number of multi-establishment firms that conduct all design activities at a single facility (sometimes referred to as a research and development (R&D) center or corporate design facility).  If the establishment scheduled for inspection is serviced by an R&D center or corporate facility, review the establishment jacket before beginning the inspection, consult the agency’s on-line OEI databases, and/or directly contact the district involved.  Determine if the home district of the R&D center or corporate design facility has conducted a design control inspection of that facility within the previous two years.  If such an inspection was conducted, it will not be necessary to conduct a design control assessment at the establishment scheduled for inspection.  If an inspection was not conducted within the previous two years, issue an assignment to the home district of the R&D center or corporate design facility requesting a design control inspection.

Some manufacturers have their devices designed under contract.  These manufacturers must comply with the requirements for using contractors or service suppliers under 21 CFR § 820.50 as well as ensuring compliance with 21 CFR § 820.30.  The manufacturer must maintain or have reasonable accessibility to copies of a Design History File for any device that is in production.

Observations relating to Design Controls placed on the FDA 483 should be limited to the adequacy of, and adherence to, the procedures and/or controls established by the firm.  Do not place observations on the FDA 483 that concern the adequacy, safety, or efficacy of a particular design.  Any such concerns should be noted in the EIR and flagged for review by the Office of Device Evaluation or the Office of In Vitro Diagnostic Devices/CDRH.

4. Special Instructions for Sterilization Processes

Sterilization Process Controls section found in the QSIT Guide is a sub-part of the Production and Process Controls subsystem.  The instructions for inspecting sterilization processes are applicable at the following types of facilities:

  • device manufacturers that sterilize their own product
  • device manufacturers that use contract sterilizers
  • contract sterilizers

NOTE: The portion of the inspection spent covering sterilization processes should be reported under PAC 82845S.

Refer to Part III, A. 6, for guidance on collection of samples relating to sterilization issues.

5. Inspection of Radiation Emitting Devices

Medical Devices which are also deemed to be “electronic products” as defined by the Federal Food Drug and Cosmetic Act, Subchapter C – Electronic Product Radiation Control, section 531(2), may be inspected under this compliance program.  These devices have additional Radiological Health requirements to protect the public from unnecessary radiation.  The requirements include the affixing of certification labeling, additional reporting and record keeping, and the continued testing to verify product conformance with applicable Federal Performance Standards promulgated under 21 CFR 1020 - 1050.  If the device being inspected is subject to Radiological Health requirements, follow the appropriate Compliance Program.  Report any Radiological Health time under the appropriate Radiological Health PAC.

When conducting QS inspections, a firm may manufacture medical devices which are capable of emitting electronic product radiation. Based on district concurrence, the firm’s devices should also be assessed against the applicable standards promulgated under Chapter V, Subchapter C - Electronic Product Radiation Control of the FD&C Act.  This assessment is not a QS activity and should not be reported as a QS activity

Use Compliance Programs 7386.001, 7386.002; and 7386.004 through 7386.007 for guidance on inspections in this area.  For Field Compliance Testing of Diagnostic Medical X-Ray Equipment, use CP 7386.003.

Device manufacturers subject to existing FDA performance standards (21 CFR Parts 1020 – 1050) should include in their device master and history records those procedures and records demonstrating compliance with the applicable standard, self-certification (21 CFR 1010), and reporting (21CFR 1002 – 1005).

6. Sample Collection

For QS, MDR, Tracking, and Correction and Removals violations, samples are not generally necessary to support a Warning Letter.  However, the District office may require, at least, a documentary sample to support even a Warning Letter.  Follow the district requirements.  Also refer to IOM Section 5.6.1.2.

Samples may be required to support further action beyond a Warning Letter.  The investigator should work with District management and compliance branch on deciding to collect samples to support QS violations. Physical samples should not be routinely collected to support QS cases. If the district should reference violative documentary or physical samples as evidence to support QS deviations, the sample should be tied to the QS deviation to show a cause/effect relationship.

Normally, the collection of samples for sterility issues is not to be performed during Level 1 (Abbreviated) inspections of device manufacturers or contract sterilizers. If sterility issues involve packaging or seam integrity, sample collection may be needed. The following items provide guidance on sampling decisions.  For questions regarding sterilization issues or the need to collect samples related to the sterilization process, contact CDRH, Office of Compliance.  Guidance on sampling decisions can be found in Part IV C.

  • Finished device samples should not routinely be collected and tested for sterility to prove quality system deficiencies in sterilization validation or process control.  Under certain circumstances, the Center may request that samples be collected for sterility testing.
  • Field examination of packaging used for sterile devices may be indicated when the assessment of packaging operations demonstrates a lack of control such that inadequate packaging is likely to occur.  Examine the packages for integrity of the sterility barrier, paying close attention to seals.
  • Samples of defective packaging found during a visual field examination, if regulatory action is contemplated for packaging deficiencies, consist of 20 sterilized packaged devices.
  • Bioburden samples are to be collected only 1) when the review of the results of bioburden testing performed by the manufacturer finds unrealistically low results; and, 2) the sterilization process is a bioburden based cycle with no safety overkill element. The sample should consist of 20 unsterilized devices.
  • Biological indicators are not to be collected routinely.  Collect 40 biological indicators only if there is reason to question the effectiveness of the indicators or under direction by the Center.
  • Endotoxin samples are to be collected only when endotoxin control is necessary for the device and when the review of the manufacturer's test methodology suggests that the manufacturer's test results may be unrealistically low.  Collect 10 sterilized devices.

If the investigator is uncertain as to whether a sample should be collected, he/she should consult with district management who may consult with the CDRH Headquarters Laboratory Liaison, WEAC, or the Division of Field Science in ORA on the laboratory capability to conduct the analysis.  (See Part VI, B. for program contacts)

B. ADDITIONAL CONSIDERATIONS

1. Registration and Listing

Registration and Listing should be reviewed as part of the pre-inspectional activities and evaluated during inspections.  Inspections should be limited to the minimum time and effort it takes to make an assessment.  Review of a random sample of device listings (less than six) and the most recent registration is adequate.  Also, randomly select two products from the firm’s catalog (or equivalent document), and determine whether listing was done. Assess whether these documents are up to date and correct.

NOTE: Registration and Listing should be covered during both domestic and foreign inspections.  Per IOM section 5.2.3.3, do not place the violative findings for registration and listing on the FDA 483, but make verbal statements to the top management about the concerns at the close-out discussion.  See Part V, Section E for regulatory considerations.

For specific guidance concerning device registration and listing requirements see IOM Subchapter 2.9 – Regulatory Submissions, section 2.9.2.1 Device Registration and Listing.  See Exhibit 5-12 for a Summary Registration and Listing requirements for medical devices.

2. Imports

No import field examinations or sample collections are scheduled under this program.

3. Exports

The FDA Export Reform and Enhancement Act of 1996 amended Section 802 of the FD&C Act to allow an establishment to export unapproved Class III devices or Class II devices not cleared and subject to mandatory standards under Section 514, to any of those countries listed in Section 802 of the Act that authorize marketing, and to any other country that recognizes the marketing authorization of a listed county without first obtaining FDA authorization.  Section 802 also requires that any such device must be manufactured in "substantial conformity with current good manufacturing practice requirements.”

Section 801(e)(1) of the Act permits the importation of adulterated or misbranded devices, components, or accessories for further processing or incorporation into a finished device, provided that the device is subsequently exported and not sold or offered for sale in domestic commerce.

Chapter 9 of the Regulatory Procedures Manual and IOM Section 6.1.2 provide guidance on “import for export”, including record keeping requirements and the types of operations that qualify as further processing or incorporation of a component into a finished device.  Exports under section 802 are subject to cGMP requirements found in the QS regulation.

Manufacturers are encouraged to make prior arrangements with their FDA district office before initiating an import for export operation. The review of the factory jacket should reveal when firms are performing such operations.  The inspection should confirm that the firm is complying with the applicable requirements of the QS regulation for exports under section 802. 

4. Electronic Records and Electronic Signatures

Follow agency policy when inspecting electronic records and signatures, see Part VI.

C. REMARKETED DEVICES

1. Remanufacturers of Used Devices

Remanufacturers are persons who process, condition, renovate, repackage, restore or do any other act to a finished device that significantly changes the finished device’s performance or safety specifications or intended use [21 CFR 820.3(w)]. Remanufacturers are considered to be manufacturers, and are subject to all applicable requirements of the Quality System regulation, MDR requirements, Device Tracking requirements, Registration and Listing, and premarket approval or clearance requirements.  If an establishment disputes its regulatory status, the district should refer the EIR to the appropriate Division of Enforcement within CDRH/OC for assistance in interpreting the definition of a remanufacturer.

NOTE:  For a discussion of the above issues see Federal Register Notice: December 23, 1997 (Volume 62, Number 246), pages 67011 – 67013.

2. Third Party Refurbishers/Reconditioners/Servicers of Used Devices

Third party refurbishers, reconditioners, servicers and "as is" resellers of used devices are currently not subject to the requirements of the Quality System regulation.  If the district receives an assignment to inspect such an establishment, the district should contact the Office of Compliance, Office of the Director, to determine the current regulatory status of such establishments.

3. Reprocessors of Single Use Devices

Third party reprocessors of single use devices are considered to be manufacturers and are subject to those requirements of the Quality System regulation that apply to the operations they perform.  See Enforcement Priorities for Single-Use Devices Reprocessed by Third Parties and Hospitals, August 14, 2000, for guidance on FDA’s enforcement strategy at the following link: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM107164

The district should contact CDRH, Office of Compliance, Office of the Director, for guidance before conducting an inspection of an establishment believed to be a third party reprocessor of single use devices, when not part of the assignment.

4. Hospital Reprocessors

Hospital reprocessors are to be only inspected under CDRH assignment.

D. REPORTING

1. General Reporting requirements are listed on the cover page. Refer to the IOM for EIR formats. Always include device, device class, and subsystems covered in the EIR.

2. QS Observations--If there are observed violations of the QS requirements, place them on the Form FDA-483.  The QSIT Guide provides guidance concerning major QS requirements and the identification of major deviations.  The most serious system deficiencies should be noted on the Form FDA-483 first, then by subsystems if possible.  Special Note: Refer to the IOM for information concerning annotation of the Form FDA-483.

3. 510(k) or PMA Observations--If the establishment does not have a valid:

  • PMA for a device that is offered for introduction into interstate commerce;
  • 510(k) for a device that was offered for introduction into interstate commerce for the first time after May 28, 1976; or,
  • Has made significant changes to a device that require a new 510(k), or PMA supplement,

then investigators should not place the observations on the Form FDA-483 unless concurrence is obtained from CDRH/OC and/or OIVD.  When Center concurrence cannot be obtained before the inspection is completed, investigators are requested to obtain complete documentation and submit that documentation for CDRH review through the district compliance branch.

4. Registration and Listing Observations -- If a firm has failed to list device(s), or to verify that their listings are up-to-date every six months and update them if they are not, as required by 21 CFR Part 807, make note of this observation(s) in the EIR for consideration for action by the district Compliance Officer.  If a firm has failed to renew its annual registration for the last two or more years as required by 21 CFR Part 807, make note of this observation in the EIR for consideration for action by the district Compliance Officer.  All registration and listing observations should be reported to firm management.

NOTE:  A firm's registration and listing status can be determined by querying the CDRH Public Registration and Listing database or by using the canned reports in the DRLM Universe in Business Objects.

Field Accomplishments and Compliance Tracking System (FACTS)--Refer to existing policy in the IOM.

5. FDA Field Accomplishments and Compliance Tracking System (FACTS)

a. When selecting specific manufacturing processes to represent profile classes, investigators should give preference to:

  • CAPA indicators of process problems
  • Process used to manufacture high risk products
  • Processes that have a high risk of causing product failure
  • Processes that require process validation
  • Processes that are new to the manufacturer
  • Processes that cover a variety of process technologies and profile classes
  • Common process used in multiple products
  • Processes not covered during previous inspections

NOTE:  If all profile classes are not directly covered during an inspection, but are covered indirectly under CAPA, then all profile classes the firm is involved with can be listed on the appropriate FACTS screen.

b. Quality System Inspections conducted should include:

(1) coverage of the device(s) specified in the assignment, or devices and related manufacturing processes representing all the same profile classes as the assigned device; and,

(2) other devices as required to provide coverage of any remaining profile classes, except QS exempt Class I devices.

c. Since the QSIT approach covers systems, the findings from the inspection can apply to all profile classes at the firm.