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ContentsSUBCHAPTER 920 - INVESTIGATION - INJURY & ADVERSE REACTION921 - INVESTIGATIONS 922 - DRUGS - INJURY OR REACTIONS 923 - DEVICES - INJURY 923.01 - Mechanical, Electrical or Electromechanical Devices 923.02 - Devices for Implant 923.03 - In Vitro Diagnostic Devices 923.04 - Investigative Procedures 924 - BIOLOGICS - INJURY, REACTION OR FATALITY 924.01 - Professional Reporting System for Vaccine Adverse Reactions 924.02 - Investigation/Reporting 925 - FOODS, DIETARY SUPPLEMENTS AND COSMETICS - INJURY OR REACTION 925.01 - Cosmetics 925.02 - Dietary Supplements 925.03 - Investigation Requirements for Serious Adverse Events of CFSAN Regulated Products 926 - VETERINARY PRODUCTS - COMPLAINTS/ADVERSE REACTIONS 927 - SAMPLE COLLECTION 928 - REPORTING SUBCHAPTER 920 - INVESTIGATION - INJURY & ADVERSE REACTION921 - INVESTIGATIONSThe purpose for investigating injury and adverse reactions to drugs, devices, biologics, foods, dietary supplements and cosmetics is to determine the cause of, and to prevent additional injury or adverse reaction to the consuming public. Injury and adverse reaction complainants should receive a prompt, courteous response, and assurance their complaints will receive appropriate consideration. An immediate follow-up should be made when there is an indication of a serious injury or adverse reaction. When investigating injuries or adverse reactions, do not make comments or enter into discussions with firms as to the involvement of particular products, unless specifically instructed to do so. Many adverse reactions come to FDA through the MedWatch system, which is operated on a voluntary basis with the reports held confidential. Divulging information before the reports are confirmed or denied is inappropriate, and not to be done. Whenever the press has been informed about a complaint, follow instructions found in Section 161. When the responsible firm invites the news media to observe the inspectional process, follow instructions found in Section 504.03. Personnel routinely receiving complaints should be particularly sensitive to those involving recently approved drugs, devices and biologics. Clinical trials may not have identified all possible adverse reactions, and FDA's approving Center may want to reconsider current labeling, modify directions for use, establish registries for monitoring, or withdraw approval based on the most recent information. Procedures - When investigating all injuries and adverse reactions:
922 - DRUGS - INJURY OR REACTIONSDrug injuries or reactions, either human or veterinary; result from the use of products which may:
Investigative Procedures - The following procedures should be followed for investigating suspected drug-induced birth defects or other adverse drug reactions:
In all cases of suspect drug-induced adverse reactions, the Center will review the information on the FDA 3500 form, and will issue assignments to the field if additional information is needed. 923 - DEVICES - INJURYThe cause of medical device injuries may originate with the manufacturer, operator, user, or from other factors including, but not limited to the transportation or installation of the device.923.01 - Mechanical, Electrical or Electromechanical DevicesInjuries caused by mechanical, electrical or electromechanical devices may result from devices that:
923.02 - Devices for ImplantCauses of injuries which may result from implanted devices include those listed in IOM 923.01. The term installation, as used above, does not include implantation. Injuries also may result because the materials used in the implant are not biocompatible, thereby causing an adverse tissue reaction and/or deterioration of the implant.923.03 - In Vitro Diagnostic DevicesCertain In Vitro Diagnostics (IVD) are instruments, such as gas chromatographs and automated blood analyzers, and much of the information under IOM 923.01 is applicable. Injuries to patients from IVD products may, in many cases, be considered indirect, because they are due to complications resulting from misdiagnosis or delays in patient treatment due to incorrect test results. Examples of IVD failures include false positives, false negatives and erratic results. Poor performance or failure may be due to poor manufacturing practices or user error. Manufacturing problems include:
User errors include:
923.04 - Investigative ProceduresWhen investigating incidents implicating a medical device, you must first confirm whether or not the device was a contributing factor. An appropriate follow-up, such as inspection at the manufacturer, may be necessary. Current agency policy defers regulation to the Department of Transportation (DOT) of automotive adaptive equipment which are medical devices. Consumer complaints or other reports concerning these devices should be referred to DOT. Copies of EIR's, FACTS Consumer Complaint Report and Follow-Up Report, including documentation and related materials, for all device consumer complaints should be sent to HFZ-343. Reports received through the Medical Device Reporting system are not considered to be consumer complaints and are tracked through a system maintained by CDRH. A FACTS Consumer Complaint Report should not be completed for any incident that CDRH has requested follow-up on via MDR, unless you originally were advised of the incident by a consumer and initiated a FACTS Consumer Complaint Report at that time. For additional information concerning MDR reports, see the applicable Compliance Program in the CPGM. Interview the victim, physician(s), and any other individual(s) who witnessed or has knowledge of the incident. When conducting an investigation at a hospital, be sure to contact and inform the administrator of the purpose of the investigation. Obtain the following information for devices:
For In Vitro Diagnostics, determine:
The report of the investigation and related documentation is extremely important and must be promptly submitted. The report will be used by CDRH Medical and Scientific Review Staff in their health hazard evaluation. For Dialysis Injury or Deaths, in addition to the general device investigative procedures,
924 - BIOLOGICS - INJURY, REACTION OR FATALITYReactions or symptoms of illness may occur in association with the administration of vaccines and other biological products. The Center for Biologics Evaluation & Research (CBER) is interested in all unexpected clinical responses to a biological product, as well as any expected responses of unusual frequency or severity. In some cases, a reaction or illness could occur because the product may:
924.01 - Professional Reporting System for Vaccine Adverse ReactionsThe National Childhood Vaccine Injury Act of 1986, 42 USC 201, was passed to achieve optimal prevention of childhood infectious diseases through immunization. At the same time, it was intended to minimize the number and severity of adverse reactions to vaccines routinely administered to children. This law requires health care providers and vaccine manufacturers to report certain adverse events which occur following the administration of specific vaccines. The vaccines and reportable events are listed in the table "Reportable Events Following Vaccination". See IOM Exhibit 920-C. The Department of Health and Human Services (DHHS) has established a Vaccine Adverse Events Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine, in all age groups, including but not limited to those in the table. The Vaccine Adverse Event Reporting System (VAERS) is administered under a joint FDA/CDC contract. The system utilizes a preaddressed and postage paid form (Form VAERS-1) for reporting adverse events which occur subsequent to vaccine administration. See IOM Exhibit 920-D. 924.02 - Investigation/ReportingWhen a biologics reaction/injury complaint is received by the district office (DO), a preliminary investigation should be conducted. CBER should be consulted before initiating any follow-up which extends beyond the complainant, and in some cases even before the complainant interview. All complaints initially received by the District Office must be recorded on the FACTS Consumer Complaint Report. When interviewing the complainant about a biologics complaint /injury, obtain:
At this point, it is generally unnecessary to conduct interviews beyond the complainant, or obtain records, until a preliminary review has been conducted. It is important to rapidly communicate the basic information about the incident, implicated product, lot, license number, manufacturer, and presence of intact units to the Center and the OCM/EOC contact. Immediately, CBER offices will advise whether reactions are expected or unexpected, and the level of investigation, including sample collection and analysis, necessary. Further follow-up is unnecessary until it has been determined the reaction/injury is not unexpected, or has not already been reported through other channels. Vaccine Products - If the complaint involves an adverse reaction of any kind, then a Form VAERS-1 (IOM Exhibit 920-D) should be sent to the complainant. The form should be completed by the complainant's physician, if at all possible, or by the complainant, if the physician will not cooperate. The completed VAERS Reporting Form should be mailed directly to the address on the form. When you send a VAERS form to a complainant, note this fact in the Remarks Section of the FACTS Consumer Complaint Report. If the complaint does not involve an adverse reaction, obtain the necessary information to allow the Center to make an informed decision on follow-up at the manufacturer. Biological Products - If the complaint is an adverse reaction to a product, an FDA 3500, MedWatch Form (See IOM Exhibit 920-A) must also be completed and forwarded to the complainant for completion by their physician. If the physician will not cooperate by completing the FDA-3500, request the complainant to do it. Assist the complainant in completing the FDA 3500, if necessary. Note in the "Remarks" section of the FACTS Consumer Complaints Report that the FDA 3500 was forwarded to the complainant. If the complaint does not involve an adverse reaction, obtain information necessary to permit the Center or home district to make an informed decision on follow-up at the manufacturer. If a complainant desires further information, refer them to CBER, Office of Biostatistics and Epidemiology at (301) 827-3974. If the complaint is a fatality where blood or a blood component is implicated, notify CBER, Office of Compliance and Biologics Quality, as soon as possible (21 CFR 606.170). This is required of the collecting facility, in the event of a donor reaction, and by the facility which performed the compatibility tests, in the event of a transfusion reaction. An investigation of the incident shall be conducted by either HCFA or FDA, based on the type of facility involved, for example, transfusion service, blood bank, plasma center or hospital. 925 - FOODS, DIETARY SUPPLEMENTS AND COSMETICS - INJURY OR REACTIONCFSAN regulates a wide variety of products including foods, seafood, wine beverages less than 7% alcohol (including wine coolers), bottled water, food additives, infant formulas, dietary supplements, and cosmetics. Each of these products is used differently and regulated under a different part of the Act and thus has slightly different investigational requirements. Background and common causes for adverse events are provided for selected products below. Monitoring of complaints on CFSAN products is performed by the CAERS Staff. CFSAN investigations are generally limited to serious adverse events. Therefore, for serious adverse events (previously defined above in IOM 902.01) follow the specific investigation requirements below, in addition to the general investigation requirements above.NOTE: Contact the Office of Scientific Analysis and Support, CFSAN Adverse Events Reporting System (CAERS) Staff, HFS-702, 301-436-2405, for all questions pertaining to field follow-up requests or medical guidance on investigations of adverse reactions associated with CFSAN monitored products. CAERS will coordinate with the office experts. 925.01 - Cosmetics Injuries or adverse reactions may arise from cosmetics which:
925.02 - Dietary Supplements
The Dietary Supplement Health and Education Act of 1994 (See DSHEA) defined the term "dietary supplement" to mean a product, intended to supplement the diet, that contains one or more dietary ingredients, i.e., vitamins, minerals, herbs or other botanicals, amino acids, and dietary substances for use by man to increase the total dietary intake, as well as a concentrate, metabolite, constituent, extract, or combination of any of the dietary ingredients. Under DSHEA, a dietary supplement is a food which must be labeled as a "dietary supplement", and cannot be represented for use as a conventional food or the sole item of a meal or diet.
DSHEA also removes dietary ingredients from coverage under the food additive provisions of the FD&C Act. Rather, DSHEA places the burden on the Agency to prove a dietary supplement or dietary ingredient is adulterated before the product can be removed from the marketplace.
Therefore, a crucial source of information on potentially unsafe products is the Agency's consumer complaint system. It is extremely important that FDA conduct appropriate investigations and follow-up on adverse events attributed to dietary supplement products.
The instruction and guidance provided below must be followed when conducting follow-up on complaints involving adverse reactions to special nutritional products.
Causes- Injuries or other adverse reactions may be associated with the use of products which:
1. Vary markedly from the declared potency or concentration.
2. Contain deleterious substances accidentally included in their manufacture.
3. Have changed composition or become contaminated after shipment.
4. Are mislabeled as to identity, warnings or instructions for use.
5. Have not been used according to label instructions or the directions of the manufacturer or prescriber.
6. Are dangerous when used according to directions.
Procedures- When investigating adverse events attributed to special nutritional products, direct attention to, and document:
1. Complete details on the product involved, including code marks.
2. The source of the offending article.
3. Details of how the product was used, including frequency, in what amounts, concomitant treatments, and whether administered by the user or someone else. Determine if label directions were followed. Obtain copies of all labeling/inserts.
4. Nature of the injury. Include any hospital or physician's records available, and identify pre-existing conditions which may have a bearing on the injury. Obtain photographs of the victim's injuries, if significant. See IOM 902.07 for the procedures used to obtain medical records.
5. Names of other persons involved, such as medical personnel, lawyers, insurance agents, etc. Obtain their views on the injury. The views of attending physician are important because they may vary markedly from those of the patient.
6. A complete description of the incident (sequence of events) and the injury.
Complete the FACTS Adverse Event Questionnaire (See IOM Exhibit 900-D) either during the initial consumer contact, e.g., telephone report of complaint, or soon thereafter. The Adverse Event Questionnaire contains additional information which must be obtained and forwarded to CFSAN. Information already contained in the FACTS Consumer Complaint Report need not be duplicated on the questionnaire.
NOTE: Contact the Office of Scientific Analysis and Support, CFSAN Adverse Events Reporting System (CAERS) Staff, HFS-702, 301-436-2405, for questions pertaining to field follow-up requests related to foods, seafood, food additives, dietary supplements, infant formulas and medical foods. CAERS personnel will coordinate field guidance related to these products with CFSAN's experts.
Questions on compliance or other regulatory matters should be directed to the Regulatory Branch, Division of Programs and Enforcement Policy (OSN), HFS-456, 202-205-5372. 925.03 - Investigation Requirements for Serious Adverse Events of CFSAN Regulated Products
1. If the suspect product is a Cosmetic, interview the injured person and/or the reporter of the event and complete the FACTS Consumer Complaint Cosmetic Report (IOM Exhibit 900-E).
2. If the suspect product is not a Cosmetic, interview the injured person and/or the reporter of the event and complete the Adverse Event Questionnaire (IOM Exhibit 900-D).
3. If suspect product is an Infant Formula or Baby Food, inform OCM/EOC 301-443-1240 immediately and investigate on a high-priority basis due to the continued sensitivity to these incidents. This will include follow-up with the doctor or hospital, sample collection and analysis of appropriate product. Refer complaints involving baby food regulated by USDA to USDA for appropriate follow-up. See IOM 910.03 and 311.02.
4. Obtain Medical Records Release forms (FDA-461) from the injured person or guardian.
5. If the adverse event is a death, the following medical records should be considered for collection:
a. Admission History and Physical or Emergency Room/Clinic record of the event if the patient was not admitted
b. Discharge Summary
c. Autopsy Report
d. Death Certificate 6. Samples - If you believe a suspect product should be sampled, discuss with your Supervisor. See IOM 902.08 for guidance.
For all events, a memo of investigation
will be completed. Send a complete copy, including copies of all labels and
labeling, Medical Records Release (FDA-461) and medical records collected
to the CAERS Staff. 926 - VETERINARY PRODUCTS - COMPLAINTS/ADVERSE REACTIONSComplaints and adverse reactions associated with veterinary products including animal drugs, medicated feeds, medical devices for animals, grooming aids (cosmetic items for animals) are handled through the Division of Surveillance (HFV-210) 301-827-6642. Veterinarians, animal owner and firms may report problems to their local FDA offices, OCM/EOC, or directly to the Center for Veterinary Medicine. The District and the OCM/EOC will complete a FACTS Consumer Complaint Report and advise the complainant to complete a FDA 1932s "Veterinary Drug Adverse Experience, Lack of Effectiveness or Product Defect Report". The form and instructions are available at www.fda.gov/cvm. For information on the history of reported problems for particular products, contact the Adverse Drug events Coordinator at the Division of Surveillance 301-827-0158. 927 - SAMPLE COLLECTIONCollect a sample of the product which caused the injury and an official sample from the same lot. Collect the same and other lot codes, if available. Check with your supervisor if you have any doubt as to the appropriateness of collecting a particular sample. See IOM 454.03 for routing of injury and complaint samples to the laboratory. Device Samples - Obtain Center concurrence prior to collecting any device samples. Biological Samples - Do not collect samples of the suspect product until an evaluation of the preliminary information on the injury/reaction has been made by CBER (Licensed products) or the Home District (Unlicensed Products, Plasma and Blood Products). Cosmetic Samples - Products such as depilatories, permanent hair dyes, home permanents, deodorants, hair straighteners, etc. are known to cause adverse reactions. Samples of these products should not be collected except in cases of alleged severe or unusual injury, e.g., multiple complaints. In case of obvious allergic type reactions, samples should not be collected. Most cosmetic products which get into the eye will cause temporary eye irritation and in such cases, a sample generally should not be collected. Collect samples associated with consumer complaints in which microbiological contamination is suspected. 928 - REPORTINGPrompt reporting is essential. You may save the lives of others. See IOM 100 English language requirement. Reporting Forms - Field personnel must report all consumer complaints in FACTS. In addition, for adverse reactions or injury associated with drugs, medical devices, cosmetics, biologics (except vaccines), provide complainants with an FDA 3500 MedWatch form (IOM Exhibit 920-A) and provide the consumer with the MedWatch web address: www.fda.gov/medwatch. Prior to sending a MedWatch form to the complainant, enter the FDA FACTS consumer complaint number in the box below the Triage Unit Sequence # in the upper right corner of form FDA 3500. For veterinary product complaints, provide complainants with an FDA 1932a "Veterinary Drug Adverse Experience, Lack of Effectiveness or Product Defect Report" available at http://www.fda.gov/cvm/default.html. For adverse reactions to vaccine products, provide complainants with form VAERS-1 (IOM 924.02, IOM Exhibit 920-D). Routing Reports - A copy of the FACTS consumer complaint report and your narrative report(s), including any copies of medical or injury reports obtained must be submitted by your district as follows: Drug complaints and injuries to: MedWatch The FDA Medical Products Reporting Program (HFD-410) Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 Medical Device & Radiological Product complaints and injuries to: Food & Drug Administration Center for Devices and Radiological Health Division of Surveillance Systems (HFZ-530) 1350 Piccard Drive Rockville, MD 20850
CFSAN regulated products including both product problems and adverse events for cosmetics, infant formulas, dietary supplements and all other foods to:
Food and Drug Administration
Center for Food Safety and Applied Nutrition/OSAS
CAERS Staff (HFS-702)
Attn: CAERS Monitor
5100 Paint Branch Pkwy
College Park, MD 20740
Veterinary injuries or adverse reaction reports to: Food and Drug Administration Center for Veterinary Medicine Division of Surveillance (HFV-210) 7500 Standish Place Rockville, MD 20857 Biologics - Licensed Products (includes vaccines), except for source plasma and blood products: The receiving district will complete the FACTS consumer complaint report and fax a copy to HFM-650 at 301-443-3874, select HFM-650 in the referrals box and then electronically forward to the home district. The home district will select "Surveillance for Next EI" as the final disposition and close the complaint. CBER will issue an assignment if follow-up is needed. Biologics - Unlicensed Product, Plasma and Blood & Blood Products: The receiving district will complete and electronically forward the FACTS consumer complaint to the home district and send a hard copy to HFM-650. The home district will determine if any follow-up is needed and issue an appropriate assignment. Advice is available from HFM-650 at (301) 594-1911. Biologics injury/adverse reaction narrative reports are forwarded to: Food and Drug Administration Center for Biologic Evaluation and Research Office of Compliance 1401 Rockville Pike, Suite 400S Rockville, MD 20852 NOTE: In addition, check the "Notify DEIO" box in FACTS for al injury and adverse reaction complaints. For serious injury/illness reports, please notify the OCM/EOC immediately at 301-443-1240.
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