General

1. What is the purpose of the APHIS/CDC Form 4A, 4B, and 4C?
   Clinical/Diagnostic Identification (Form 4A)
   

   Any person or entity, including any clinical or diagnostic laboratory, having identified a select agent or toxin contained in a specimen or sample presented for diagnosis or verification is required by the select agent regulations (7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73) to report this identification by submitting a completed and signed APHIS/CDC Form 4A to either AgSAS or DSAT. This form can be found at the Federal Select Agent Program website (http://www.selectagents.gov/form4.html).

   Proficiency Testing Identification (Form 4B)

   Any person or entity, including any clinical or diagnostic laboratory, having identified a select agent or toxin contained in a specimen or sample presented for proficiency testing is required by the select agent regulations to report this identification by submitting a completed and signed APHIS/CDC Form 4B to either AgSAS or DSAT. This form can be found at the Federal Select Agent Program website (http://www.selectagents.gov/form4.html).

   Federal Law Enforcement Seizure (Form 4C)
   

   A Federal law enforcement agency that seizes a select agent or toxin is required by the select agent regulations to report this seizure by submitting a completed and signed APHIS/CDC Form 4C to either AgSAS or DSAT. This form can be found at the Federal Select Agent Program website (http://www.selectagents.gov/form4.html).

2. Our entity is a diagnostic/clinical laboratory whose activities involving select agents and toxins are limited to diagnosis, verification, and proficiency testing. Do we meet the exemption provisions of Select Agent Regulations?

   Anyone that possesses a select agent or toxin that is contained in a diagnostic or verification specimen or sample is exempt from the requirements of the select agent regulations for that specific select agent or toxin if you do the following:

   • Unless directed otherwise by AgSAS or DSAT, within seven (7) calendar days after identification of the select agent or toxin, either transfer the select agent or toxin in accordance with section 16 of the select agent regulations (requires prior approval by AgSAS or DSAT) or destroy the specimen on-site by a recognized sterilization or inactivation process.
   • Before transfer or destruction, secure the select agent or toxin to prevent theft, loss, or release.
   • Immediately report the identification of specific select agents and toxins listed in the regulations (See immediate notification list). Additionally, an APHIS/CDC Form 4A should be sent to the CDC or APHIS Select Agent Program needs to be AgSAS or DSAT within seven (7) calendar days after identification.
   • Maintain copies of all APHIS/CDC Form 4A reports for a period of (3) three years.

   
   

   Anyone that possesses a select agent or toxin that is contained in a specimen used as a part of proficiency testing is also exempt from the requirements of the select agent regulations only for that specific specimen and only if you do the following:

   • Unless directed otherwise by AgSAS or DSAT, within ninety (90) days of receipt of the sample or specimen used for proficiency testing, either transfer the select agent or toxin in accordance with section 16 of the select agent regulations (includes prior approval by AgSAS or DSAT) or destroy the specimen on-site by a recognized sterilization or inactivation process.
   • Before transfer or destruction, secure the select agent or toxin to prevent theft, loss, or release.
   • Send an APHIS/CDC Form 4B to the AgSAS or DSAT within ninety (90) days of receipt of the proficiency testing sample or specimen. It is important to note that the ninety (90) days starts from the date you receive the proficiency test and not from the date you identify the select agent.
   • The entity maintains a completed APHIS/CDC Form 4B for a period of three years.

   
   

   NOTE: The retention of a diagnostic, verification, or proficiency sample which has been identified as positive for a select agent by an individual or entity that is not registered with either AgSAS or DSAT is a violation of Federal law. Such possession would include the retention of a select agent or toxin which had been identified from a diagnostic, verification, or proficiency specimen as a positive control or reference sample.

3. Is there any guidance available to address the day-to-day operations of diagnostic laboratories in human, animal, and plant diagnostic laboratories?

   Recommendations from a CDC-convened, Biosafety Blue Ribbon Panel were published in the Morbidity and Mortality Weekly Report entitled "Guidelines for Safe Work Practices in Human and Animal Medical Diagnostic Laboratories." This document is available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/su6101a1.htm?s_cid=su6101a1_w . Additional information on this topic can be found in the CDC/NIH Biosafety in Microbiological and Biomedical Laboratories manual and the NIH Guidelines for Research Involving Recombinant DNA Molecules. Additional reference information for plant diagnostic labs may be found at https://www.npdn.org/login.

4. Our diagnostic laboratory is not registered to possess a Tier 1 select agent or toxin, may we receive identified Tier 1 select agents and toxin?

   No, the laboratory is not registered to possess a Tier 1 select agent or toxin.

5. Can our laboratory receive a Tier 1 select agent or toxin to destroy it if we are not registered with the Federal Select Agent Program as long as it is within the 7 days of identification?

   No, the laboratory is not registered to possess a Tier 1 select agent or toxin.

6. Is a select toxin identified in an original food sample or clinical sample as a result of diagnosis or verification required to be reported on APHIS/CDC Form 4?

   Yes. Original food samples and clinical samples are those specimens that are submitted to laboratories for diagnosis or verification purposes to identify or verify a select agent or toxin. For example, an original food sample could be a container of potato salad or juice. An original clinical sample could be serum or stool from a patient.

7. Is waste generated during the delivery of care for a patient diagnosed with an illness or condition associated with a select agent subject to select agent regulations (SAR)?

   It depends. Waste generated during the care of a patient diagnosed with a condition associated with a select agent is not subject to SAR if it is decontaminated or transferred for destruction according to state and federal regulations within seven calendar days of the conclusion of care.

Diagnosis and Verification

1. Is any amount of a select toxin identified as a result of diagnosis or verification required to be reported on APHIS/CDC Form 4?

   Regardless of the amount identified, clinical and diagnostic laboratories that identify a select toxin contained in a sample presented for diagnosis or verification must report the identification of the toxin in accordance with 42 CFR § 73.5 (a)(7).

2. Is a registered entity required to report select agents or toxins identified from clinical/diagnostic specimens?

   Yes. In accordance with Section 9(c) of the select agent regulations, the Responsible Official must report the identification and final disposition of any select agent or toxin contained in a specimen presented for diagnosis or verification. The registered entity does have the option of adding the identified or verified select agent or toxin to their registration.

3. What Form do I complete if I have identified a select agent or toxin in a clinical sample?

   You would complete APHIS/CDC Form 4A reporting the identification of a select agent or toxin from a clinical/diagnostic specimen (section A: Reference Laboratory Information and section B: Select Agent or Toxin Identified from Clinical/Diagnostic Specimen (s)) within seven calendar days of identification of a select agent or toxin as a result of diagnosis or verification. This form can be found at the National Select Agent Program website (http://www.selectagents.gov/form4.html).

4. When completing the APHIS/CDC Form 4A, what should I list under sample type (s) received/provided?

   Under the APHIS/CDC Form 4A block B5 and APHIS/CDC Form 4A block D4 the following are acceptable sample types to be used:

   • Human Clinical/Diagnostic sample – a sample (not the isolate) that was directly derived from an individual human (e.g., blood, sputum, tissue).
   • Human Isolate – a purified culture obtained from a specimen or sample taken from a human (e.g., slant, plate, etc.).
   • Animal Clinical/Diagnostic sample – a sample (not the isolate) that was directly derived from an individual animal (e.g., blood, sputum, tissue).
   • Animal Isolate – a purified culture obtained from a specimen or sample taken from an animal (e.g., slant, plate, etc.).
   • Plant Diagnostic sample – a sample (not the isolate) that was directly derived from an individual plant or group of plants (e.g., sap (xylem or phloem), tissue, seed or other fruiting body, other plant part(s), etc.).
   • Plant Isolate – a purified culture or purified material obtained from a sample taken from a plant (e.g., slant, plate, DNA, RNA, etc.).
   • Environmental sample – a sample that was not directly derived from a human, animal, or plant (e.g., water sample, soil sample, air sample).
   • Food Sample – a sample that was directly derived from a food source, food container or food by-product (e.g., can of soup, beans, milk).

   
   
5. How long may a non-registered laboratory keep a diagnostic specimen of a presumptive select agent sent to a reference laboratory for confirmation?

   A diagnostic specimen may be kept by the sending non-registered laboratory until the identification of a select agent or toxin. After the identification, the non-registered laboratory must either:
   (1) Destroy the specimens (diagnostic specimen containing the select agent). If the choice is to destroy the select agent or toxin, the date and method of destruction must be indicated on the APHIS/CDC Form 4A; or
   (2) Transfer the specimens (diagnostic specimen containing the select agent) to an entity registered for the select agent(s) or toxin(s). Prior to the transfer, pre-approval must be obtained by submitting APHIS/CDC Form 2 ("Request to Transfer of Select Agents or Toxins") to AgSAS or DSAT.

6. If a patient produces multiple specimens, do I need to submit a separate APHIS/CDC Form 4A for each sample?

   No. You would complete one APHIS/CDC Form 4A Reporting the identification of a select agent or toxin from a clinical/diagnostic specimen section A: Reference Laboratory Information and section B: Select Agent or Toxin Identified from Clinical/Diagnostic Specimen (s). This information would be listed in Section B and should include the number and type of samples received (e.g., tissue, fluid, urine, etc.), the zip code of the patient’s residence and if additional samples are anticipated.

7. After identification, is a laboratory able to retain the isolate that contains a select agent?

   If the laboratory is registered with CDC or APHIS Select Agent Program for the identified select agent(s) and toxin(s), the laboratory may retain the isolate that contains the select agent. Note: The registered laboratory must still account for the new addition in its records in accord with the select agent regulations.

8. How would the registered entity note on the APHIS/CDC Form 4A that it retains the sample?

   In Section B7 of the APHIS/CDC Form 4A, the entity would check “retained” and list the name of the person that took responsibility of the material.

9. Is the APHIS/CDC Form 2 required to transfer select agents or toxins identified from clinical/diagnostic specimens being sent for susceptibility testing?

   Yes, APHIS/CDC Form 2 would be required to request prior authorization for the transfer of the identified select agent(s) or toxin(s). For further guidance regarding requesting a transfer of a select agent or toxins, please refer to: http://www.selectagent.gov/form2.html.

10. Our laboratory is not registered to possess Tier 1 select agents and toxin and we have identified a Tier 1 select agent through diagnosis and verification testing. Do we meet the exemption provisions of Select Agent Regulations?

    Yes, as long as the entity fulfills all of the requirements outlined in Sections 5 and 6 in select agent regulations regarding a select agent or toxin that is contained in a diagnostic or verification specimen or sample.

Proficiency Testing

1. Does the sender/sponsor need an APHIS/CDC Form 2 when sending a specimen for proficiency testing that contains a select agent or toxin?

   No. A select agent or toxin that is contained in a specimen for proficiency testing may be transferred without prior authorization from AgSAS or DSAT provided that, at least seven calendar days prior to the transfer, the sponsor/sender provides information to AgSAS or DSAT the select agent or toxin to be transferred and the name and address of the recipient.

2. What section do I complete if I have identified a select agent or toxin in a proficiency test?

   You would complete APHIS/CDC Form 4B Reporting the identification of a select agent or toxin: Proficiency testing report within ninety days of receipt.

3. Our laboratory is not registered to possess Tier 1 select agents and toxin and we have identified a Tier 1 select agent through proficiency testing. Do we meet the exemption provisions of Select Agent Regulations?

   Yes, as long as the entity fulfills all of the requirements outlined in Sections 5 and 6 in select agent regulations regarding a select agent or toxin that is contained in a sample presented for proficiency testing.