(a) ICSR reporting—(1) General. Except as provided in paragraph (c) of this section, applicants and nonapplicants must submit each ICSR associated with the use of a designated medical gas in humans described in paragraph (b) of this section to FDA as soon as possible but no later than 15 calendar days from the date when the applicant or nonapplicant has met the reporting criteria described in paragraph (b) of this section and acquired a minimum data set for an ICSR for an adverse event.
(2) Copies of ICSRs obtained from FDA. An applicant or nonapplicant should not resubmit under this section any ICSRs obtained from FDA's adverse event reporting database or forwarded to the applicant or nonapplicant by FDA.
(3) Followup information. Applicants and nonapplicants must submit any new information that is related to a previously submitted ICSR or an ICSR that was sent to the applicant or nonapplicant by FDA no later than 15 calendar days after the information is received or otherwise obtained.
(b) Reporting requirements—(1) Serious adverse events—(i) Reported to or otherwise received by the applicant or nonapplicant. Applicants and nonapplicants must submit ICSRs for serious adverse events reported to or otherwise received by the applicant or nonapplicant (such as a report initiated by a patient, consumer, or healthcare professional, or received at the request of the applicant or nonapplicant).
(ii) Reported from the scientific literature. Applicants and nonapplicants must submit ICSRs for serious adverse events obtained from published scientific and medical journals either as case reports or as the result of a formal clinical trial.
(iii) Exception to reporting requirements for serious adverse events. Notwithstanding paragraphs (b)(1)(i) and (ii) of this section, ICSRs are not required for reports of the death of a patient who was administered oxygen, unless the applicant or nonapplicant is aware of evidence to suggest that the death was caused by the administration of oxygen.
(2) Other adverse event reports to be submitted upon notification by FDA. Upon notification by FDA, applicants and nonapplicants must submit, in a timeframe established by FDA, ICSRs for any adverse events that are not required under paragraph (b)(1) of this section. The notification will specify the adverse events to be reported and the reason for requiring the reports.
(c) Completing and submitting ICSRs. This paragraph (c) describes how to complete and submit ICSRs required under this section.
(1) Electronic format for submissions. (i) ICSRs and ICSR attachments must be in an electronic format that FDA can process, review, and archive.
(ii) An applicant or nonapplicant may request, in writing, a temporary waiver of the requirements in paragraph (c)(1)(i) of this section. These waivers will be granted on a limited basis for good cause shown.
(2) Submitting ICSRs—(i) Single submission of each ICSR. Submit each ICSR only once.
(ii) Separate ICSR for each patient. The applicant or nonapplicant must submit a separate ICSR for each patient who experiences an adverse event reportable under paragraph (b) of this section.
(iii) Coding terms. The adverse event terms described in the ICSR must be coded using standardized medical terminology.
(iv) Minimum data set. All ICSRs submitted under this section must contain at least the minimum data set for an ICSR for an adverse event. The applicant or nonapplicant must actively seek the minimum data set in a manner consistent with the written procedures under paragraph (f) of this section. Applicants and nonapplicants must document and maintain records of their efforts to obtain the minimum data set.
(v) ICSR elements. The applicant or nonapplicant must complete all known, available elements of an ICSR as specified in paragraph (d) of this section.
(A) For adverse events, applicants and nonapplicants must actively seek any information needed to complete all applicable elements, consistent with their written procedures under paragraph (f) of this section.
(B) Applicants and nonapplicants must document and maintain records of their efforts to obtain the missing information.
(vi) Supporting documentation. An applicant or nonapplicant must submit the following types of supporting documentation in an ICSR, if available:
(A) A copy of the autopsy report if the patient died, or a copy of the hospital discharge summary if the patient was hospitalized. The applicant or nonapplicant must submit each document as an ICSR attachment. The ICSR attachment must be submitted either with the initial ICSR or no later than 15 calendar days after obtaining the document. English translations of foreign language documents must be provided.
(B) A copy of the published article as an ICSR attachment for each ICSR of an adverse event obtained from the published scientific and medical literature. Foreign language articles must be accompanied by an English translation of the abstract. When submitting more than one ICSR from the same published article, the applicant or nonapplicant must submit only one copy of the article with one of the ICSRs. For the remaining ICSRs not accompanied by a copy of the published article, the applicant or nonapplicant must include the cross-reference to the specific ICSR to which the article is attached.
(d) Information reported on ICSRs. ICSRs must include the following information, subject to paragraph (c)(2)(v) of this section:
(1) Patient information, which includes:
(i) Patient identification code;
(ii) Patient age at the time of adverse event, or date of birth;
(iii) Patient sex; and
(iv) Patient weight.
(2) Adverse event, which includes:
(i) Outcome attributed to adverse event;
(ii) Date of adverse event;
(iii) Date of ICSR submission;
(iv) Description of adverse event;
(v) Adverse event term(s);
(vi) Description of relevant tests conducted, including dates and laboratory data; and
(vii) Other relevant patient history, including preexisting medical conditions.
(3) Suspect designated medical gas(es), which includes:
(i) Name;
(ii) Dose, frequency, and route of administration used;
(iii) Therapy dates;
(iv) Diagnosis for use (indication);
(v) Whether the adverse event abated after the use of the designated medical gas(es) stopped or the dose was reduced;
(vi) Whether the adverse event reappeared after reintroduction of the designated medical gas(es);
(vii) Lot number;
(viii) National Drug Code (NDC) number; and
(ix) Concomitant medical products and therapy dates.
(4) Initial reporter information, which includes:
(i) Name, address, email address, and telephone number;
(ii) Whether the initial reporter is a healthcare professional; and
(iii) Occupation, if a healthcare professional.
(5) Applicant or nonapplicant information, which includes:
(i) Applicant or nonapplicant name, address, email address, and telephone number;
(ii) Report source, such as spontaneous, literature, or study;
(iii) Date the report was received by applicant or nonapplicant;
(iv) New drug application and/or new animal drug application number;
(v) Whether the ICSR is an expedited report;
(vi) Whether the ICSR is an initial report or followup report; and
(vii) Unique case identification number, which must be the same in the initial report and any subsequent followup report(s).
(e) Recordkeeping. (1) For a period of 10 years from the initial receipt of information, each applicant or nonapplicant must maintain records of information relating to adverse events under this section, whether or not submitted to FDA.
(2) These records must include raw data, correspondence, and any other information relating to the evaluation and reporting of adverse event information that is received or otherwise obtained by the applicant or nonapplicant.
(3) Upon written notice by FDA, the applicant or nonapplicant must submit any or all of these records to FDA within 5 calendar days after receipt of the notice. The applicant or nonapplicant must permit any authorized FDA employee, at reasonable times, to access, copy, and verify these established and maintained records described in this section.
(f) Written procedures. The applicant or nonapplicant must develop written procedures needed to fulfill the requirements in this section for the surveillance, receipt, evaluation, and reporting to FDA of adverse event information, including procedures for employee training and for obtaining and processing adverse event information from other applicants and nonapplicants.
(g) Patient privacy. An applicant or nonapplicant should not include in reports under this section the names and addresses of individual patients; instead, the applicant or nonapplicant should assign a unique code for identification of the patient. The applicant or nonapplicant should include the name of the reporter from whom the information was received as part of the initial reporter information, even when the reporter is the patient. As set forth in FDA's public information regulations in part 20 of this chapter, FDA generally may not disclose the names of patients, individual reporters, healthcare professionals, hospitals, and geographical identifiers submitted to FDA in adverse event reports.
(a) Report for adverse events. This report provides information on each adverse event associated with the use of a designated medical gas in animals, regardless of the source of the information.
(1) Serious adverse events. The applicant or nonapplicant must submit serious adverse events to FDA as soon as possible but no later than within 15 calendar days of first receiving the information. The report must be submitted to the Agency in electronic format as described in paragraph (b)(1) of this section, unless the applicant or nonapplicant obtains a waiver under paragraph (b)(2) of this section or FDA requests the report in an alternate format.
(i) Reported to or otherwise received by the applicant or nonapplicant. Applicants and nonapplicants must submit reports for each serious adverse event reported to or otherwise received by the applicant or nonapplicant (such as reports initiated by a patient, consumer, veterinarian, or other healthcare professional, or received at the request of the applicant or nonapplicant), regardless of whether the applicant or nonapplicant believes the events are related to the designated medical gas.
(ii) Reported from the scientific and medical literature. Applicants and nonapplicants must submit reports for each serious adverse event obtained from the published scientific and medical literature regardless of whether the applicant or nonapplicant believes the events are related to the designated medical gas.
(iii) Exception to reporting requirements for serious adverse events. Notwithstanding paragraphs (a)(1)(i) and (ii) of this section, reports are not required to be submitted for the death of an animal that was administered oxygen, unless the applicant or nonapplicant becomes aware of evidence to suggest that the death was caused by the administration of oxygen.
(2) Other adverse event reports to be submitted upon notification by FDA. Upon notification by FDA, applicants and nonapplicants must submit reports of adverse events associated with the use of a designated medical gas in animals that do not qualify for reporting under paragraph (a)(1) of this section. The notice will specify the adverse events to be reported and the reason for requiring the reports.
(3) Copies of adverse event reports obtained from FDA. An applicant or nonapplicant should not resubmit under this section any adverse event reports obtained from FDA's adverse event reporting database or forwarded to the applicant or nonapplicant by FDA.
(b) Format for submissions—(1) Electronic submissions. Reports submitted to FDA under this section must be submitted in an electronic format that FDA can process, review, and archive. Data provided in electronic submissions must be in conformance with the data elements in Form FDA 1932 and FDA technical documents describing transmission. As necessary, FDA will issue updated technical documents on how to provide the electronic submission (e.g., method of transmission and processing, media, file formats, preparation and organization of files). Unless requested by FDA, paper copies of reports submitted electronically should not be submitted to FDA.
(2) Waivers. An applicant or nonapplicant may request, in writing, a temporary waiver of the electronic submission requirements in paragraph (b)(1) of this section. The initial request may be provided by telephone or email to the Center for Veterinary Medicine's Division of Pharmacovigilance and Surveillance, with prompt written followup submitted as a letter to the granted certification(s). FDA will grant waivers on a limited basis for good cause shown. If FDA grants a waiver, the applicant or nonapplicant must comply with the conditions for reporting specified by FDA upon granting the waiver.
(c) Records to be maintained. (1) For a period of 5 years from the initial receipt of information, each applicant or nonapplicant must maintain records of information relating to adverse event reports under this section, whether or not submitted to FDA.
(2) These records must include raw data, correspondence, and any other information relating to the evaluation and reporting of adverse event information that is received or otherwise obtained by the applicant or nonapplicant.
(3) Upon written notice by FDA, the applicant or nonapplicant must submit any or all of these records to FDA within 5 calendar days after receipt of the notice. The applicant or nonapplicant must permit any authorized FDA employee, at reasonable times, to access, copy, and verify these established and maintained records described in this section.