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
- 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.
- 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).
- 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
- 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.
- 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:
- Be brief and concise and still cover the necessary aspects
of the inspection;
- Be factual, objective and free of personal conclusions; conclusions
should be limited to the proposed endorsement;
- Not contain trivial episodes not related to the inspection
unless there is a specific reason for reporting them;
- Be written in the first person;
- 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: http://www.fda.gov/ora/compliance_ref/rpm_new2/ch10.html.
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:
intranet.fda.gov/oirm/manuals/forms/all_forms.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:
-
Guide to Inspection of International Medical Device Manufacturers
(5/96)
-
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.
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