• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

  • Print
  • Share
  • E-mail

Section Contents Menu

Inspections

Chapter 3 ESTABLISHMENT INSPECTIONS (340-390)

Chapter 3 ESTABLISHMENT INSPECTIONS

Subchapters 340 - 390
Drugs, Devices, Biologic Products,
Bioresearch, Inspection Reporting, Sampling

 

CONTENTS

 

Subchapter 340 DRUGS
    340.1 General
341 DRUG REGISTRATION AND LISTING
342 PROCEDURE
343 DISTRIBUTION AND DOMESTIC FOLLOW UP
344 CONTRACT FACILITIES

SubChapter 350 DEVICES
    350.1 General
351 DEVICE REGISTRATION AND LISTING
352 PROCEDURE
353 DISTRIBUTION AND DOMESTIC FOLLOW-UP
354 CONTRACT FACILITIES
355 INSPECTION INFORMATION
    355.1 Pre-inspection Activity
    355.2 510(K) Class III Devices
    355.3 PMA Devices
    355.4 Electronic Product Radiation Producing Devices
    355.5 High Risk Devices
    355.6 Designated Agent
356 DOCUMENTATION
357 DISCUSSION WITH MANAGEMENT
358 REINSPECTION OF AUTOMATIC DETENTION FIRMS
359 EXPEDITED REVIEW OF VIOLATIVE FINDINGS

Subchapter 360 BIOLOGIC PRODUCTS
361 BIOLOGIC REGISTRATION AND LISTING
362 PROCEDURE

Subchapter 370 BIORESEARCH

Subchapter 380 INSPECTION REPORTING
    380.1 General
    380.2 Responsibility
381 FACTS COVERSHEET AND REPORTING
382 NARRATIVE REPORT
    382.1 Non-violative Establishments
    382.2 Violative Establishments
    382.3 Individual Captions and other Information for the EIR
383 REPORT PROCESSING
384 DATA REPORTING IN FACTS
385 RESPONSIBILITY
386 INSPECTIONAL REFERENCES

Subchapter 390 SAMPLING
    390.1 SAMPLE COLLECTION FOR PREAPPROVAL INSPECTIONS
    390.2 RECEIPT FOR SAMPLES
    390.3 PAYMENT OF SAMPLES
391 SHIPMENT OF SAMPLES

CHAPTER 3 EXHIBITS
FDA-483 Inspectional Observations Policy

 SUB CHAPTER 340 DRUGS

 340.1 GENERAL

The purpose of inspections of foreign drug manufacturers is to ensure that drugs are manufactured according to the procedures and formulations specified in the approval submissions, and according to Current Good Manufacturing Practice (CGMP) Regulations.
All Regulations, Compliance Programs and Guidelines apply equally to foreign and domestic drug firms. These should be used as a guide for inspection, although all reporting/sampling requirements in Compliance Programs may not be practical or possible.

Meticulous preparation prior to departure for an international drug inspection trip is most important. This preparation should include
the review of previous EIRs, available profile sheets, NDAs, abbreviated NDAs, Drug Master Files (DMF), antibiotic applications (Forms 5/6), NADAs and complaints.

Make necessary copies of pages from DMFs, NDAs, ANDAs, NADAs, Antibiotic Applications, etc., prior to departure. Do not carry original documents when traveling.

Be familiar with current programs relating to drugs and current FDA policies. During the briefing be alert for specific items of interest by the reviewing chemists. Make copies of all reference materials, which may be needed during the trip (e.g., USP, Remington's, Industrial Sterilization, etc.).

See IOM Section 540.

 341 DRUG REGISTRATION AND LISTING

Foreign drug establishments are now required to register and list their products with FDA, CDER. Refer to Part 207 of the Code of Federal Regulations (CFR) Title 21 for background guidance on requirements for listing. Be alert for products being offered for export or actually being exported into the U.S. that are not on the firm's current Drug Listing.

Prior to departure, review the Drug Listing information available for the firms you are going to inspect to determine what products the firm may be exporting to the U.S. Encourage firms to update Drug Listing information.

See IOM Section 541.

 342 PROCEDURE

Inspections should be comprehensive, with specific coverage of the product(s) in question (NDA/ANDA approval, specific assignments, etc.). You should also perform a general evaluation of the firm's entire operation including other drug processes and products, (all profile classes) manufactured in the firm's facilities at the location. This includes other drugs, medical device or biologic products. This information can be important in determining any cross contamination potential from another room, area, floor, or even a separate building.

In evaluating a drug manufacturer's Quality Control System, be aware that many standards besides the USP/National Formulary (NF) exist. Evaluate specifications for products and compare them to what is required by the USP/NF.

 343 - DISTRIBUTION AND DOMESTIC FOLLOW-UP

Report all products manufactured (including material that is not a drug or for drug use) and indicate which products are exported to the U.S. Also obtain and report identification of all products manufactured at the site, and volume of production of products exported to the U.S.

If the inspection appears to be violative, immediately relay information regarding all U.S. consignees and specific shipments of the products involved to DFI. The investigator should fully document all deficiencies with exhibits, production records, etc. Clearly report any cross contamination potential observed and the products subject to such cross contamination.

 344 CONTRACT FACILITIES

On occasion, inspections of contract facilities are necessary. These establishments may be blenders, sterilizers, testing labs, etc. These firms are extensions of the manufacturing facility. Evaluate the contract facility's adherence to applicable GMPs. They should be reported separately with individual EIRs and unique Firm Establishment Inventory (FEI) number and not reported as part of the manufacturer's EIR.

Be cognizant of operations that may be performed at a contract facility but may not be described in the relevant application(s) or DMF. If identified, describe the situation and operations performed in the EIR for the firm being inspected.

The scope of inspection of a contract facility covers only operations involving products belonging to the manufacturing facility. However, the depth of inspection may be extended in order to evaluate the contract facility's adherence to GMPs.

Be cautious regarding any discussions with employees of a contract facility. Some information is confidential or a trade secret and may not be known by the contract facility.

 SUB CHAPTER 350 DEVICES

 350.1 GENERAL

The purpose of inspections of foreign medical device manufacturers is to ensure that devices are manufactured according to the procedures and formulations specified in the premarket notification submissions, and according to QS/GMP Regulations.

All Regulations, Compliance Programs and Guidelines apply equally to foreign and domestic medical device firms.

Meticulous preparation prior to departure for an international device inspection trip is most important. This preparation should include the review of previous EIRs, available profile sheets, PMA's (when applicable), 510(K) submissions, Medical Device Reporting (MDR), and recall information.

Be familiar with current issues and concerns related to devices and current FDA policies. Be alert for specific items, which may be of interest to reviewers of the PMA's or 510(k)'s. Make copies of all reference materials, which may be needed during the trip (i.e. Industrial Sterilization, Association for the Advancement of Medical Instrumentation (AAMI) standards, Guidances for Industry and Guides to Inspections, etc.).

Medical device inspections should be conducted according to all applicable Compliance Programs. Each inspection of a foreign device manufacturer should include a thorough QS/GMP inspection with emphasis on certain key points. Refer to the current guides to inspections.

See IOM Section 550.

 351 DEVICE REGISTRATION AND LISTING

All foreign device manufacturers who export their devices into the U.S. are required to register and list their devices with FDA, CDRH. Refer to 21 CFR Part 807.

 352 PROCEDURE

Refer to the IOM, Part 800 of the CFR, and applicable Compliance Programs regarding conduct of EI's of device and in vitro diagnostic manufacturers.

DFI will provide copies of previous EIRs, PMAs, etc. to the investigator prior to departure. Investigators will sometimes be scheduled for a briefing at headquarters to meet with CDRH reviewers regarding specific issues. However, this may not always be necessary. When so advised, travelers will leave directly from their home duty station.

 353 - DISTRIBUTION AND DOMESTIC FOLLOW-UP

Report all products manufactured, their classification, and indicate volume distributed in the U.S. and the U.S. consignees.

If the inspection appears to be violative, report all U.S. distributors and specific shipments of products involved.

 354 CONTRACT FACILITIES

Medical device manufacturers may employ the services of outside contractors such as laboratories, sterilization facilities, or other processors. In such cases, the finished device manufacturer is responsible for assuring that these contractors comply with the GMP's and that the product or service provided is adequate. These contractors will be subject to FDA inspection and the GMP regulations. They should be treated as separate firms, with individual EIRs and unique FEIs.

See IOM Section 555.

 355 – INSPECTION INFORMATION

Each inspection of a foreign device manufacturer should include a thorough QS/GMP inspection in accordance with current Compliance Programs with emphasis on the following key points.

 355.1 – PRE-INSPECTIONAL ACTIVITY

The MDR database should be reviewed prior to starting the inspection. A trend analysis can be performed of the data to determine
whether there are any potential product and/or process problems. These can provide focus during the inspection. Printouts of MDR reports can be provided as part of the pre-inspection package from DFI.

In certain circumstances, prior to performing the inspection, DFI may arrange for an in-house or telephone briefing for the investigator with the Field Program’s Branch HFZ-306 and/or other CDRH reviewers. The purpose of the briefing is to make the investigator aware of problems with specific companies or products, and to provide inspectional guidance as needed. Other CDRH reviewers (such as MDR, and recall reviewers) may also provide a briefing.

See IOM Section 551.1.

 355.2 - 510(K) CLASS III DEVICES

A number of Class III device inspections will cover devices, which are marketed via a 510(K) premarket notification. The inspection should determine whether all devices being shipped to the U.S. have a 510(K), which has been found substantially equivalent. For these devices, it should be determined if the company is complying with any product and/or process specifications listed in the 510(K). Also, if significant product and/or process changes have occurred, it should be determined if a new 510(K) has been submitted.

In some cases, the initial importer submits the 510(K) and the foreign manufacturer may not see the submission. If so, determine who the initial importers of the device are.

In addition, some inspections may be driven by the 510(K) preclearance inspection Program. In these instances, the investigator must FAX a short summary of inspectional findings, along with the FDA 483 (if issued) to HFC-130 and HFZ-306 immediately after the inspection.

 355.3 – PMA DEVICES

Some inspections will be for premarket approval (PMA) devices. The inspection may be a pre-approval type for either an original PMA or a PMA supplement or it may be a post-market inspection. In either instance, the inspection must be conducted in accordance with Compliance Program 7383.001. The investigator will be provided with the appropriate manufacturing sections of the PMA.

Some routine inspections will be conducted for PMA devices, which have previously received clearance, and are not subject to the post-approval inspection criteria of the Compliance Program. These inspections should determine if the company is manufacturing, and shipping to the U.S., any variations of the device which do not have PMA clearance. Also, it should be determined if there are any significant changes in either the device’s design or in the manufacturing process, and whether PMA clearance has been obtained for these, or whether the manufacturing site has changed.

Fax a short summary of inspection findings along with the FDA-483, if issued, to HFC-130 and HFZ-306 immediately after the inspection.

 355.4 – ELECTRONIC PRODUCT RADIATION PRODUCING DEVICES

During the inspection, determine whether the firm manufacturers any devices subject to Sub Chapter C – Electronic Product Radiation Control, formerly the Radiation Control Health and Safety Act (RCHSA). If so, determine whether the firm has submitted initial reports. Are any of the devices subject to performance standards? If so, are they meeting the performance standards? Determine whether the firm reported all Accidental Radiation Occurrences (AROs) to FDA. Determine whether the firm performed any Corrective Action Plans (CAPS) without notifying FDA.

 355.5 – HIGH RISK DEVICES

If any devices previously described as significant risk or critical (see the Compliance Program for the list) are being manufactured for export to the U.S., these should be given priority coverage.

See IOM Section 551.2.

 355.6 – DESIGNATED AGENT

The inspection should determine who is the designated agent (U.S.) for each device. The EIR must include the complete name, address and phone number of the initial distributors and the specific device(s) distributed by each must be identified. This information is vital for determining MDR reporting requirements. Foreign firms are subject to MDR and they are required to register. However, in cases where there is joint ownership and control, knowledge of a reportable event by the foreign manufacturer may be imputed to its U.S. subsidiary, i.e., the designated agent. In these cases, the designated agent is subject to reporting when it becomes aware that its foreign manufacturer has information that meets the threshold requirements of MDR.

Foreign firms that are owned or jointly controlled by a U.S. firm are subject to MDR. If a U.S. firm provides the foreign firm with device specifications then this is considered to be joint control. If the U.S. firm owns part of the foreign firm and has the right to dictate policy, orders, etc., then this is considered to be joint ownership.

During the inspection, the designated agent should be identified for all MDR reportable complaints found. Also determine whether the foreign firm has received any complaints from initial distributors.

 356 – DOCUMENTATION

  1. FDA 483 – Each listed observation should be clear and concise. The facts should be clearly stated so that, if the company chooses, they can respond appropriately to the pertinent observation. The use of the draft Turbo EIR FDA-483 citation language is encouraged. A copy may be obtained from DFI.
  2. EIR – Make certain that each item on the FDA 483 is fully discussed in the report. Where possible, documentation should be collected to support each observation (even if the documentation is in a foreign language).
  3. All EIRs must include the FAX number of the foreign manufacturers, if available. Written correspondence, e.g., Warning letters will be mailed and Faxed to foreign manufacturers simultaneously. Faxing the correspondence is necessary to assure that the foreign manufacturer receives the correspondence before it is available under FOI.

 357 – DISCUSSION WITH MANAGEMENT

During the discussion, do not under any circumstances indicate any inspectional conclusions.

All discussions regarding FDA 483 observations should be made in accordance with IOM 516.

If no FDA 483 is issued, inform the firm that the establishment report is subject to further review. Keep in mind that FDA483 observations may be determined to be non-supportable upon further review, and in instances where no FDA 483 is issued, further review may disclose significant deviations which could result in a regulatory action.

If the firm indicates that a response to FDA 483 Inspectional Observations will be sent to the agency, inform the firm that all responses must: a. include documentation supporting and/or showing corrections, (e.g., records, data) and b. all records and documents must be translated into English.

 358 – REINSPECTION OF AUTOMATIC DETENTION FIRMS

  1. If the reinspection has clearly determined that the foreign manufacturer has made corrections and no FDA-483 is issued, then FAX a short note to HFC-130, (301) 443-6919 and HFZ-306, (301) 594-4715 stating the same and that the firm should be removed from automatic detention. Identify exactly what, if any, devices should be removed from automatic detention and what should remain on automatic detention. After receipt of the Faxed information, HFZ-306 will inform the appropriate Division of Enforcement within the Office of Compliance, HFZ-300, of the inspectional findings. They will notify Import Operations, HFC-170, that the automatic detention should be removed.
  2. Foreign Manufacturers should remain on automatic detention if the reinspection results in the issuance of a FDA 483, which contains significant continuing, and/or new GMP deviations. If this is the case, then a short note should be Faxed to HFC-130 and HFZ-306, stating the same and specifying whether any device should be added or removed from the ongoing automatic detention.

A foreign manufacturer may be considered for removal from automatic detention when a FDA 483 contains minor deviations and the reinspection has determined that adequate corrections have been made regarding GMP deviations which resulted in the Warning Letter and Automatic detention.

 359 – EXPEDITED REVIEW OF VIOLATIVE FINDINGS

If an inspection has clearly determined that a foreign manufacturer has significant system-wide QS/GMP deviations, the FDA 483 and a summary of findings should be faxed to HFC-130 and HFZ-306. If possible, a few exhibits, (if in English) would be helpful. After receipt of the faxed information, HFZ-306 will inform the Office of Compliance, HFZ-300, in order that a review of the findings can be expedited prior to completion of the final Establishment Inspection Report (EIR). This will enable streamlining of the issuance of a Warning Letter and potential Automatic Detention.

 SUB CHAPTER 360 BIOLOGIC PRODUCTS

The purpose of inspections of foreign manufacturers of blood and blood products is to ensure that biologic products are manufactured according to the CGMP regulations and procedures specified in premarket applications submitted to the Agency.

 361 - BIOLOGIC REGISTRATION AND LISTING

See IOM Section 773 & 562.

 362 - PROCEDURE

Refer to the IOM (Section 561) and the 21 CFR (210-211, 600-680 and 820), FDA Policies which include guidance to the blood and blood products industry, The Compliance Policy Guides Chapter 2, and applicable Compliance Programs regarding conduct of EI's of manufacturers of blood and blood products.

DFI will provide copies of previous EIRs, etc. to the investigator prior to departure.

 SUB CHAPTER 370 - BIORESEARCH

Inspectional activities in the bioresearch monitoring include biopharmaceutics, Good Laboratory Practice (GLP), sponsor/monitor, clinical investigators, Institutional Review Boards (IRBs). In most instances, inspections conducted under these program areas will be done on assignment from and with the assistance of a staff member from HFD 344/ HFD 345, Division of Scientific Investigations. Refer to the Compliance Programs for each of these areas. Become familiar with all associated regulations.

During these inspections, the investigator is the team leader. Refer to IOM Section 502.4 regarding the responsibilities of a team leader.

 SUB CHAPTER 380 – INSPECTION REPORTING

 380.1 GENERAL

Upon completion of each inspection, send a facsimile message to DFI, International Operations Branch at (301) 443-6919 or (301) 827-6685. Include a copy of the FDA-483 and a short summary of findings. Report any violative findings for QS or GMP inspections in FACTS, as soon as you return to your home district. Notify potential OAI findings to the appropriate Center immediately to expedite approval/non-approval of applications and/or initiate appropriate action.

The content of an EIR will vary according to the nature and seriousness of violations encountered. The EIR should:

  1. Be brief and concise and still cover the necessary aspects of the inspection;
  2. Be factual, objective and free of personal conclusions; conclusions should be limited to the proposed endorsement;
  3. Not contain trivial episodes not related to the inspection unless there is a specific reason for reporting them;
  4. Be written in the first person;
  5. Make sure the inspection data is entered accurately in FACTS.

The Investigator/Analyst should inquire of firm management what their intentions are regarding correction of objectionable conditions. Report in FACTS/CARS, any voluntary corrections made while the inspection was ongoing. Also report all corrections made to objectionable conditions noted during the previous EI.

 380.2 - RESPONSIBILITY

The investigator should complete a FACTS cover sheet for each inspection and prepare a narrative report with all-necessary documents and exhibits. The EIR should be submitted to the immediate supervisor for endorsement.

The team leader should advise each team member of their reporting responsibilities and prepare the summary of findings and submit the complete final report.

Time is allocated in each itinerary so that EIR's can be prepared immediately following each inspection. If the firm is violative and product is currently being exported to the U.S., submit draft EIRs immediately to DFI while in travel status instead of waiting to return to the U.S. Coversheets, profile forms, exhibits, etc. should be held until the completed and signed EIR is submitted.

The travel voucher should be prepared and submitted to the regional/district auditor within 5 days after return from travel. To expedite shipment, overnight courier should be used.

 381 – FACTS COVER SHEET AND REPORTING

Refer to the IOM, Section 592, for a detailed discussion and preparation guidance regarding the cover sheets. Use the instructions in the IOM with appropriate PAC to report time on all international EIs. The following points have been highlighted as an extra reminder:

  • DFI has the responsibility for issuing FEIs for foreign firms. Contact DFI when inspecting a new firm, or any other firm that does not have a FEI.
  • Assignments are entered in FACTS by DFI personnel and assigned to the travelers. Do not generate foreign assignments in under the ADHOC method.
  • All PAC codes used for international inspections are the same as for domestic inspections.
  • The endorsement for each inspection should include the reason and the source for the inspection, a brief history of previous inspectional findings including the classification of the previous inspection, a statement regarding corrective actions, a concise summary and evaluation of current findings.

Be specific in stating exactly what products were covered. State clearly whether the firm should be considered "acceptable" or "unacceptable" for the particular profile class covered where applicable. Do not make this sort of statement in any portion of the narrative report, including the Summary of Findings. A firm may be acceptable for one profile class and unacceptable for another. Specify profile classes covered with the appropriate codes. Avoid using the word "approvable" as this is reserved for applications which are approved by FDA.

The district will enter all Inspection Conclusion/Classification codes and make the final recommendation.

 382 NARRATIVE REPORT

Follow the guidelines established in the IOM Section 593. Special instructions may specify, or good judgment may dictate that some captions be omitted, expanded, or added to cover subject areas. In any case, explain in detail specifically what products and what systems, or areas were or were not covered during the inspection. This will help in planning future inspections and will aid in the subsequent review of the report.

All reports should be submitted within the required timeframe. Refer to website: RPM Chapter 10 - Narrative Procedures.

 382.1 NONVIOLATIVE ESTABLISHMENTS (IOM Section 593.1)

Abbreviated EIR's may be prepared for all non-violative inspections, unless it is an initial inspection. Follow the Summary of Findings requirements in the IOM.

 382.2 VIOLATIVE ESTABLISHMENTS

Describe all objectionable conditions or practices. Fully develop all captions, which are necessary to document the violative conditions. Be certain each FDA 483 item is thoroughly discussed.

See IOM 593.2.

 382.3 INDIVIDUAL CAPTIONS AND OTHER INFORMATION FOR THE EIR

In addition to appropriate standard domestic EIR information, the following should be included in the report of foreign establishments:

  • Under the appropriate caption include the firm's FAX and telephone number.
  • Under the caption "Persons Inter-viewed," record the names, titles and specific address for the designated individuals to whom official FDA correspondence will be sent.
  • Report the U.S. agent or contact for the firm including name, phone number, fax number, affiliation.
  • Under the caption "Volume of Production," list the volume of production of products covered during the current inspection. Specify amount of each product made for the U.S. market. Also report other products made at the facility, not intended for the U.S.
  • Under caption "Logistics" or "Accommodations" include any pertinent information related to the location of the firm, method and time of transportation, or any other facts that would be helpful for future inspections. Include comments on specific lodging or specific cities where convenient lodging and food can be found.
  • Individual Responsibility It is not necessary to spend a lot of time developing individual responsibilities. It will be sufficient to list the key responsible individuals of the firm and who supplied relative information.
  • Under the caption "Corrective Actions" explain in detail what has been done or what has not been done regarding each point on any Form FDA 483, List of Observations, issued during the previous inspection. Also complete the appropriate portion of the FDA - 481 (CG).

If the firm's manufacturing process remains as reported in documents such as in DMFs, NDAs, PMAs or schedule processes, it is not necessary to describe the firm's manufacturing process but simply refer to those document(s). If a system (e.g. raw materials, water, batch records, etc.) is adequate and in control, simply state that fact. There is no need to fully describe such operations.

Include a discussion of voluntary corrections and report this information on the cover sheet under Compliance Activities Reporting.

Any information, which is not relevant to the firm but may be of interest to, DFI or other FDA units, should be reported by separate memo, through DFI.

Collect exhibits only when a definite purpose is served. It is possible that fewer exhibits may be collected during international inspections than domestic inspections.

Do not collect, as exhibits, copies of supplements to DMFs, NDAs, etc., or offer to make submissions to FDA for the firm. Advise the firm that they should submit these documents to the appropriate unit in headquarters.

Stay in contact with other FDA investigators to keep abreast of current inspectional methods.

 383 REPORT PROCESSING

Upon request, DFI will type EIRs in rough draft when submitted on dictated tapes. The draft EIRs will be sent (on disks or e-mail) to the traveler's duty station. Investigator(s)/ analyst(s) will sign the final and submit it, with all typed computer generated coversheets (including endorsement) profile sheets, attachments, and any exhibits, to the district supervisor for endorsement. The district supervisor or International Operations Group member (for headquarters staff) will review the inspection reports and prepare endorsements. Submit finalized EIRs as follows:

  • Human Drug - Completed original of EIR with endorsement, FACTS coversheets, FDA-483, recommendation and draft document for proposed action (import alert, Warning Letter, seizure, etc.) will be sent to CDER/OC/FIT (HFD-322). Send a copy (without exhibits) to DFI/IOB (HFC-130). All such documents should be sent by overnight delivery service.
  • Medical Device - Completed EIR with endorsement, FACTS coversheets, FDA-483, profile data sheet, recommendation for proposed action (import alert, Warning Letter, seizure, etc.) will be sent to CDRH/OC/FPB (HFZ-306). Send a copy without exhibits to DFI/IOB (HFC-130). All such documents should be sent by overnight delivery service.
  • Veterinary Drugs - Completed EIR with proposed endorsement, FACTS coversheets, FDA-483, etc. will be sent to CVM/HFV-142. Send a copy without exhibits to DFI/IOB (HFC-130).
  • Food/Low Acid Canned Food - Completed EIR with proposed endorsement, FACTS coversheets, FDA-483, etc. will be sent to DFI/IOB (HFC-130) for concurrence and distribution.
  • Biologic and Blood Products - Completed EIR with proposed endorsement, FACTS coversheets, plus Exhibits FDA-483, etc. will be sent via Federal Express to CBER, Division of Inspection and Surveillance, WOC Building, Room 400S, HFM-650 Rockville, MD 20857. The Fax number to CBER is (301) 594-1944. Additional copy (without exhibits) should be sent via Federal Express to DFI at 5600 Fishers Lane, Rockville, MD 20857 Rm. 13-71, HFC-130. The Fax number to DFI is (301) 443-6919 or (301) 827-6685.
  • MQSA - Completed EIR with proposed endorsement, FACTS coversheets, FDA-483, etc. will be sent to DFI/Medical Device Group (HFC-130) for concurrence and distribution.
  • WEAC - Completed EIR with proposed endorsement, FACTS coversheets, FDA-483, etc. will be sent to DFI/Medical Device Group (HFC-130) for concurrence and distribution.

EIRs should be completed promptly and in accordance with guidance provided in Field Management Directive No. 86, or within 30 working days from the date of the inspection.

The responsibility for issuing the inspected firm a copy of their EIR when an inspection is deemed closed will, for the most part, be the responsibility of the appropriate Center. See FMD 145.

 384 - DATA REPORTING IN FACTS

The objective of this chapter is to assure accurate reporting/recording of data relating to international inspectional activities. Accurate data for international activities is equally as important as that reported for domestic operations. This information is necessary in order to track violative firms, Compliance Achievements (CARS) recorded in FACTS, to assure proper follow up activities, project future operations, and project budget needs, etc. Refer to IOM Section 591.1

 385 RESPONSIBILITY

All international inspectional data must be reported in accordance with procedures outlined in the IOM. In the past, a significant number of international EIRs have gone unreported and/or unclassified. International inspection Field Accomplishments and Compliance Tracking System (FACTS) data should be entered in the investigator's home district. The assignments are entered in FACTS by DFI.

The Program Assignment Code(s) (PAC) for international inspections " XXR806" used in the past have been eliminated beginning FY 99. All international inspections are reported against the appropriate domestic PAC. The PAC code(s) are included in the FACTS assignment by DFI. The operation code for international inspections is "11."

Be aware that FACTS reporting is imperative in order to recoup funds from Prescription Drug User Fees (PDUFA). Refer to Inspection Planner forms provided by DFI for appropriate reporting codes to be used for each inspection.

If an inspection is conducted by a team, e.g. Investigator/Analyst, assure that both individuals properly report time in FACTS. The Investigator/Analyst should each submit data to their respective district data processing unit. The responsibility for indicating inspection conclusions and district decisions varies by program area as follows:

Human Drugs - Lead Investigator's District Office

Veterinary Drugs – Lead Investigator’s District

Medical Devices - Lead Investigator's District
Office

MQSA - Lead Investigator's District Office (as part of automated program)

Food/Low -Acid Canned Food - DFI

Blood and Blood Products/ Fractionators - DFI

Joint ORA/CBER Inspections for Vaccines, Allergenics, Therapeutics and Blood Bank Reagent Manufacturers - CBER, Office of Compliance, Inspections Task Force

If, upon final review, the respective Center, Office of Compliance, changes the classification of an EIR, the DIB will be provided with information regarding the change. This information should be used to update the classification with the district DPU.

Refer to website:
http://inside.fda.gov:9003/Administrative/Forms/FDA/default.htm to access any FDA forms you need.

When the firm is new and does not have a Firm Establishment Inventory (FEI) number, the investigator should contact DFI to have one assigned.

The Investigator must enter profile information into FACTS. Upon review of the EIR, if there is a change in the firm's status, the Center (CDER/OC or CDRH/OC) will submit updated profile classifications to (MPQAS).

Also be guided by Data Codes Manual, refer to website: web.ora.fda.gov/dpem/Evaluation/data_codes_manual/Table_of_Contents.htm

 386 - INSPECTIONAL REFERENCES

A number of references are available and should be utilized during international inspections. These include, but are not limited to: The IOM, Chapter 10 Guides to Inspections, Investigational Training Manual, etc. These documents can be obtained electronically via the internet at: http://www.fda.gov/ora/ under inspectional references.

The following is a list of guides published by DFI for use as inspections references:

  1. Guide to Inspection of International Medical Device Manufacturers (5/96)
  2. Guideline to ICH Q7A for APIs (7/01)

 SUB CHAPTER 390 – SAMPLING

 390.1 - SAMPLE COLLECTION FOR PREAPPROVAL INSPECTIONS

Preapproval New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) inspections may require the collection of a forensic sample (finished dosage form, all associated active ingredients and excipients). Be guided by Appendix B - CP 7356.002F, the assignment and appropriate compliance program regarding when and what samples to collect during an international inspection. When forensic sample is collected, they are sent to FCC (Forensic Chemistry Center) for analyses.

There may be rare situations wherein the investigator will be called upon by DFI to collect a sample (e.g., follow up to a botulism case, potentially counterfeit drugs, etc.). DFI will provide all necessary information and support where appropriate.

 390.2 - RECEIPT FOR SAMPLES

If a sample is to be collected at the foreign firm, be guided by the procedures in the IOM Section 412 and Exhibit 410-B for an example of a Receipt for Samples (Form FDA 484).

 390.3 - PAYMENT OF SAMPLES

Be guided by the IOM Section 416 in regards to payment for samples. Cost of samples should be paid with funds withdrawn by ATM. Always obtain a receipt for the cost of samples. If the sample cost is excessive, you should contact DFI for further guidance.

 391 - SHIPMENT OF SAMPLES

Since it is not prudent, or convenient to carry samples from country to country (especially drug samples), request the firm to provide packing materials and assistance in preparing the samples for shipment.

Samples must be officially sealed.

Ship the samples directly to yourself at your official duty station. Identifying samples, C/R's, etc. is too time consuming to do in international travel status. You should complete the necessary forms and ship samples to the appropriate lab upon your return. Use Federal Express or other express carrier. Shipping charges are reimbursable.

Do not allow the firm to pack unsealed samples without your supervision and do not allow the firm to pay for the shipping.

If samples require special handling (e.g. refrigeration, frozen, etc.) coordinate with the firm for assistance in packing and shipping the sample. Also make proper arrangements for storage of the sample upon receipt in the U.S.