Title 21—Food and Drugs--Volume 1
PART 1271—HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS
§ 1271.1   What are the purpose and scope of this part?
(a) Purpose. The purpose of this part, in conjunction with §§ 207.9(a)(5), 210.1(c), 210.2, 807.20(d), and 820.1(a) of this chapter, is to create an electronic registration and listing system for establishments that manufacture human cells, tissues, and cellular and tissue-based products (HCT/P's) and to establish donor-eligibility, current good tissue practice, and other procedures to prevent the introduction, transmission, and spread of communicable diseases by HCT/P's.
(b) Scope. (1) If you are an establishment that manufactures HCT/P's that are regulated solely under the authority of section 361 of the Public Health Service Act (the PHS Act), this part requires you to register and list your HCT/P's with the Food and Drug Administration's (FDA's) Center for Biologics Evaluation and Research and to comply with the other requirements contained in this part, whether or not the HCT/P enters into interstate commerce. Those HCT/P's that are regulated solely under the authority of section 361 of the PHS Act are described in § 1271.10.
(2) If you are an establishment that manufactures HCT/P's that are regulated as drugs, devices and/or biological products under section 351 of the PHS Act and/or the Federal Food, Drug, and Cosmetic Act, §§ 207.9(a)(5) and 807.20(d) of this chapter require you to register and list your HCT/P's following the procedures in part 207 (if a drug and/or biological product) of this chapter or part 807 (if a device) of this chapter. Sections 210.1(c), 210.2, 211.1(b), and 820.1(a) of this chapter require you to comply with the donor-eligibility procedures in subpart C of this part and the current good tissue practice procedures in subpart D of this part, in addition to all other applicable regulations.
§ 1271.3   How does FDA define important terms in this part?
The following definitions apply only to this part:
(a) Autologous use means the implantation, transplantation, infusion, or transfer of human cells or tissue back into the individual from whom the cells or tissue were recovered.
(b) Establishment means a place of business under one management, at one general physical location, that engages in the manufacture of human cells, tissues, and cellular and tissue-based products. “Establishment” includes:
(1) Any individual, partnership, corporation, association, or other legal entity engaged in the manufacture of human cells, tissues, and cellular and tissue-based products; and
(2) Facilities that engage in contract manufacturing services for a manufacturer of human cells, tissues, and cellular and tissue-based products.
(c) Homologous use means the repair, reconstruction, replacement, or supplementation of a recipient's cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor.
(d) Human cells, tissues, or cellular or tissue-based products (HCT/Ps) means articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. Examples of HCT/Ps include, but are not limited to, bone, ligament, skin, dura mater, heart valve, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen or other reproductive tissue. The following articles are not considered HCT/Ps:
(1) Vascularized human organs for transplantation;
(2) Whole blood or blood components or blood derivative products subject to listing under parts 607 and 207 of this chapter, respectively;
(3) Secreted or extracted human products, such as milk, collagen, and cell factors; except that semen is considered an HCT/P;
(4) Minimally manipulated bone marrow for homologous use and not combined with another article (except for water, crystalloids, or a sterilizing, preserving, or storage agent, if the addition of the agent does not raise new clinical safety concerns with respect to the bone marrow);
(5) Ancillary products used in the manufacture of HCT/P;
(6) Cells, tissues, and organs derived from animals other than humans; and
(7) In vitro diagnostic products as defined in § 809.3(a) of this chapter.
(8) Blood vessels recovered with an organ, as defined in 42 CFR 121.2, that are intended for use in organ transplantation and labeled “For use in organ transplantation only.”
(e) Manufacture means, but is not limited to, any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cell or tissue, and the screening or testing of the cell or tissue donor.
(f) Minimal manipulation means:
(1) For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue's utility for reconstruction, repair, or replacement; and
(2) For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues.
(g) Transfer means the placement of human reproductive cells or tissues into a human recipient.
(h) Biohazard legend appears on the label as follows and is used to mark HCT/Ps that present a known or suspected relevant communicable disease risk.
(i) Blood component means a product containing a part of human blood separated by physical or mechanical means.
(j) Colloid means:
(1) A protein or polysaccharide solution, such as albumin, dextran, or hetastarch, that can be used to increase or maintain osmotic (oncotic) pressure in the intravascular compartment; or
(2) Blood components such as plasma and platelets.
(k) Crystalloid means an isotonic salt and/or glucose solution used for electrolyte replacement or to increase intravascular volume, such as saline solution, Ringer's lactate solution, or 5 percent dextrose in water.
(l) Directed reproductive donor means a donor of reproductive cells or tissue (including semen, oocytes, and embryos to which the donor contributed the spermatozoa or oocyte) to a specific recipient, and who knows and is known by the recipient before donation. The term directed reproductive donor does not include a sexually intimate partner under § 1271.90.
(m) Donor means a person, living or dead, who is the source of cells or tissue for an HCT/P.
(n) Donor medical history interview means a documented dialog about the donor's medical history and relevant social behavior, including activities, behaviors, and descriptions considered to increase the donor's relevant communicable disease risk:
(1) With the donor, if the donor is living and able to participate in the interview, or
(2) If not, with an individual or individuals able to provide the information sought in the interview (e.g., the donor's next-of-kin, the nearest available relative, a member of the donor's household, an individual with an affinity relationship, and/or the primary treating physician).
(o) Physical assessment of a cadaveric donor means a limited autopsy or recent antemortem or postmortem physical examination of the donor to assess for signs of a relevant communicable disease and for signs suggestive of any risk factor for a relevant communicable disease.
(p) Plasma dilution means a decrease in the concentration of the donor's plasma proteins and circulating antigens or antibodies resulting from the transfusion of blood or blood components and/or infusion of fluids.
(q) Quarantine means the storage or identification of an HCT/P, to prevent improper release, in a physically separate area clearly identified for such use, or through use of other procedures, such as automated designation.
(r) Relevant communicable disease agent or disease means:
(1)(i) For all human cells and tissues, a communicable disease or disease agent listed as follows:
(A) Human immunodeficiency virus, types 1 and 2;
(B) Hepatitis B virus;
(C) Hepatitis C virus;
(D) Human transmissible spongiform encephalopathy, including Creutzfeldt-Jakob disease; and
(E) Treponema pallidum.
(ii) For viable, leukocyte-rich cells and tissues, a cell-associated disease agent or disease listed as follows:
(A) Human T-lymphotropic virus, type I; and
(B) Human T-lymphotropic virus, type II.
(iii) For reproductive cells or tissues, a disease agent or disease of the genitourinary tract listed as follows:
(A) Chlamydia trachomatis ; and
(B) Neisseria gonorrhea.
(2) A disease agent or disease not listed in paragraph (r)(1) of this section:
(i) For which there may be a risk of transmission by an HCT/P, either to the recipient of the HCT/P or to those people who may handle or otherwise come in contact with it, such as medical personnel, because the disease agent or disease:
(A) Is potentially transmissible by an HCT/P and
(B) Either of the following applies:
( 1 ) The disease agent or disease has sufficient incidence and/or prevalence to affect the potential donor population, or
( 2 ) The disease agent or disease may have been released accidentally or intentionally in a manner that could place potential donors at risk of infection;
(ii) That could be fatal or life-threatening, could result in permanent impairment of a body function or permanent damage to body structure, or could necessitate medical or surgical intervention to preclude permanent impairment of body function or permanent damage to a body structure; and
(iii) For which appropriate screening measures have been developed and/or an appropriate screening test for donor specimens has been licensed, approved, or cleared for such use by FDA and is available.
(s) Relevant medical records means a collection of documents that includes a current donor medical history interview; a current report of the physical assessment of a cadaveric donor or the physical examination of a living donor; and, if available, the following:
(1) Laboratory test results (other than results of testing for relevant communicable disease agents required under this subpart);
(2) Medical records;
(3) Coroner and autopsy reports; and
(4) Records or other information received from any source pertaining to risk factors for relevant communicable disease (e.g., social behavior, clinical signs and symptoms of relevant communicable disease, and treatments related to medical conditions suggestive of risk for relevant communicable disease).
(t) Responsible person means a person who is authorized to perform designated functions for which he or she is trained and qualified.
(u) Urgent medical need means that no comparable HCT/P is available and the recipient is likely to suffer death or serious morbidity without the HCT/P.
(v) Act means the Federal Food, Drug, and Cosmetic Act.
(w) PHS Act means the Public Health Service Act.
(x) FDA means the Food and Drug Administration.
(y) Adverse reaction means a noxious and unintended response to any HCT/P for which there is a reasonable possibility that the HCT/P caused the response.
(z) Available for distribution means that the HCT/P has been determined to meet all release criteria.
(aa) Complaint means any written, oral, or electronic communication about a distributed HCT/P that alleges:
(1) That an HCT/P has transmitted or may have transmitted a communicable disease to the recipient of the HCT/P; or
(2) Any other problem with an HCT/P relating to the potential for transmission of communicable disease, such as the failure to comply with current good tissue practice.
(bb) Distribution means any conveyance or shipment (including importation and exportation) of an HCT/P that has been determined to meet all release criteria, whether or not such conveyance or shipment is entirely intrastate. If an entity does not take physical possession of an HCT/P, the entity is not considered a distributor.
(cc) Establish and maintain means define, document (in writing or electronically), and implement; then follow, review, and, as needed, revise on an ongoing basis.
(dd) HCT/P deviation means an event:
(1) That represents a deviation from applicable regulations in this part or from applicable standards or established specifications that relate to the prevention of communicable disease transmission or HCT/P contamination; or
(2) That is an unexpected or unforeseeable event that may relate to the transmission or potential transmission of a communicable disease or may lead to HCT/P contamination.
(ee) Importer of record means the person, establishment, or its representative responsible for making entry of imported goods in accordance with all laws affecting such importation.
(ff) Processing means any activity performed on an HCT/P, other than recovery, donor screening, donor testing, storage, labeling, packaging, or distribution, such as testing for microorganisms, preparation, sterilization, steps to inactivate or remove adventitious agents, preservation for storage, and removal from storage.
(gg) Quality audit means a documented, independent inspection and review of an establishment's activities related to core CGTP requirements. The purpose of a quality audit is to verify, by examination and evaluation of objective evidence, the degree of compliance with those aspects of the quality program under review.
(hh) Quality program means an organization's comprehensive system for manufacturing and tracking HCT/Ps in accordance with this part. A quality program is designed to prevent, detect, and correct deficiencies that may lead to circumstances that increase the risk of introduction, transmission, or spread of communicable diseases.
(ii) Recovery means obtaining from a human donor cells or tissues that are intended for use in human implantation, transplantation, infusion, or transfer.
(jj) Storage means holding HCT/Ps for future processing and/or distribution.
(kk) Validation means confirmation by examination and provision of objective evidence that particular requirements can consistently be fulfilled. Validation of a process, or process validation , means establishing by objective evidence that a process consistently produces a result or HCT/P meeting its predetermined specifications.
(ll) Verification means confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.
(mm) Importer means a company or individual in the United States that is the owner, consignee, or recipient, at the time of entry, of the foreign establishment's HCT/P that is imported into the United States.
(nn) United States agent means a person residing or maintaining a place of business in the United States whom a foreign establishment designates as its agent. This definition excludes mailboxes, answering machines or services, or other places where an individual acting as the foreign establishment's agent is not physically present.
§ 1271.10   Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part, and if so what must I do?
(a) An HCT/P is regulated solely under section 361 of the PHS Act and the regulations in this part if it meets all of the following criteria:
(1) The HCT/P is minimally manipulated;
(2) The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer's objective intent;
(3) The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and
(4) Either:
(i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
(ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:
( a ) Is for autologous use;
( b ) Is for allogeneic use in a first-degree or second-degree blood relative; or
( c ) Is for reproductive use.
(b) If you are a domestic or foreign establishment that manufactures an HCT/P described in paragraph (a) of this section:
(1) You must register with FDA;
(2) You must submit to FDA a list of each HCT/P manufactured; and
(3) You must comply with the other requirements contained in this part.
§ 1271.15   Are there any exceptions from the requirements of this part?
(a) You are not required to comply with the requirements of this part if you are an establishment that uses HCT/P's solely for nonclinical scientific or educational purposes.
(b) You are not required to comply with the requirements of this part if you are an establishment that removes HCT/P's from an individual and implants such HCT/P's into the same individual during the same surgical procedure.
(c) You are not required to comply with the requirements of this part if you are a carrier who accepts, receives, carries, or delivers HCT/P's in the usual course of business as a carrier.
(d) You are not required to comply with the requirements of this part if you are an establishment that does not recover, screen, test, process, label, package, or distribute, but only receives or stores HCT/P's solely for implantation, transplantation, infusion, or transfer within your facility.
(e) You are not required to comply with the requirements of this part if you are an establishment that only recovers reproductive cells or tissue and immediately transfers them into a sexually intimate partner of the cell or tissue donor.
(f) You are not required to register or list your HCT/P's independently, but you must comply with all other applicable requirements in this part, if you are an individual under contract, agreement, or other arrangement with a registered establishment and engaged solely in recovering cells or tissues and sending the recovered cells or tissues to the registered establishment.
§ 1271.20   If my HCT/P's do not meet the criteria in § 1271.10, and I do not qualify for any of the exceptions in § 1271.15, what regulations apply?
If you are an establishment that manufactures an HCT/P that does not meet the criteria set out in § 1271.10(a), and you do not qualify for any of the exceptions in § 1271.15, your HCT/P will be regulated as a drug, device, and/or biological product under the act and/or section 351 of the PHS Act, and applicable regulations in title 21, chapter I. Applicable regulations include, but are not limited to, §§ 207.9(a)(5), 210.1(c), 210.2, 211.1(b), 807.20(d), and 820.1(a) of this chapter, which require you to follow the procedures in subparts C and D of this part.
§ 1271.21   When do I register, submit an HCT/P list, and submit updates?
(a) You must register and submit a list of every HCT/P that your establishment manufactures within 5 days after beginning operations or within 30 days of the effective date of this regulation, whichever is later.
(b) You must update your establishment registration annually in December, except as required by § 1271.26. You may accomplish your annual registration in conjunction with updating your HCT/P list under paragraph (c) of this section.
(c)(i) If no change described in § 1271.25(c) has occurred since you previously submitted an HCT/P list, you are not required to update your listing.
(ii) If a change described in § 1271.25(c) has occurred, you must update your HCT/P listing with the new information:
( a ) At the time of the change, or
( b ) Each June or December, whichever month occurs first after the change.
§ 1271.22   How do I register and submit an HCT/P list?
(a) You must use the electronic registration and listing system at http://www.fda.gov/cber/tissue/tisreg.htm in accordance with § 1271.25 for:
(1) Establishment registration,
(2) HCT/P listings, and
(3) Updates of registration and HCT/P listing.
(b) FDA will periodically issue guidance on recommended procedures for providing registration and listing information in electronic format (for example, method of transmission, media, file formats, preparation, and organization of files).
(c) You must provide the information under paragraph (a) of this section in accordance with part 11 of this chapter, except for the requirements in § 11.10(b), (c), and (e) and the corresponding requirements in § 11.30.
§ 1271.23   How is a waiver from the electronic format requirements requested?
(a) You may request a waiver from the requirement in § 1271.22 that information must be provided to FDA in electronic format. Submission of a request for waiver does not excuse timely compliance with the registration and listing requirements. FDA will grant a waiver request if FDA determines that the use of electronic means for submission of registration and listing information is not reasonable for the registrant making the waiver request.
(b) Waiver requests under this section must be submitted in writing and must include the specific reasons why electronic submission is not reasonable for the registrant and a U.S. telephone number and mailing address where FDA can contact the registrant. Waiver requests may be sent to the Center for Biologics Evaluation and Research (CBER), Document Control Center (see addresses in § 600.2 of this chapter).
(c) If FDA grants the waiver request, FDA may limit its duration and will specify terms of the waiver and provide information on how to submit establishment registration, listings, other information, and updates, as applicable.
§ 1271.25   What information is required for establishment registration and HCT/P listing?
(a) Your establishment registration must include:
(1) The legal name(s) of the establishment;
(2) Each physical location, including the street address, telephone number, email address, and the postal service ZIP code of the establishment;
(3) The name, address, telephone number, email address, and title of the reporting official;
(4) A dated signature by the reporting official affirming that all information contained in the establishment registration and HCT/P listing form is true and accurate, to the best of his or her knowledge.
(5) Each foreign establishment must also submit the name, address, telephone number, and email address of each importer that is known to the establishment, and the name of each person who imports or offers for import such HCT/P to the United States for purposes of importation; and
(6) Each foreign establishment must also submit the name, address, telephone number, and email address of its United States agent.
(i) The United States agent must reside or maintain a place of business in the United States.
(ii) Upon request from FDA, the United States agent must assist FDA in communications with the foreign establishment, respond to questions concerning the foreign establishment's products that are imported or offered for import into the United States, and assist FDA in scheduling inspections of the foreign establishment. If the Agency is unable to contact the foreign establishment directly or expeditiously, FDA may provide information or documents to the United States agent, and such an action is equivalent to providing the same information or documents to the foreign establishment.
(iii) The foreign establishment or the United States agent must report changes in the United States agent's name, address, telephone number, or email address to FDA within 30 calendar days of the change.
(b) Your HCT/P listing must include all HCT/P's (including the established name and the proprietary name) that you recover, process, store, label, package, distribute, or for which you perform donor screening or testing. You must also state whether each HCT/P meets the criteria set out in § 1271.10.
(c) Your HCT/P listing update must include:
(1) A list of each HCT/P that you have begun recovering, processing, storing, labeling, packaging, distributing, or for which you have begun donor screening or testing, that has not been included in any list previously submitted. You must provide all of the information required by § 1271.25(b) for each new HCT/P.
(2) A list of each HCT/P formerly listed in accordance with § 1271.21(a) for which you have discontinued recovery, processing, storage, labeling, packaging, distribution, or donor screening or testing, including for each HCT/P so listed, the identity by established name and proprietary name, and the date of discontinuance. We request but do not require that you include the reason for discontinuance with this information.
(3) A list of each HCT/P for which a notice of discontinuance was submitted under paragraph (c)(2) of this section and for which you have resumed recovery, processing, storage, labeling, packaging, distribution, or donor screening or testing, including the identity by established name and proprietary name, the date of resumption, and any other information required by § 1271.25(b) not previously submitted.
(4) Any material change in any information previously submitted. Material changes include any change in registration and listing information, submitted, such as whether the HCT/P meets the criteria set out in § 1271.10.
(d) If your HCT/P is described under § 1271.20 and is regulated under a BLA, you must submit the information required under part 207 of this chapter using the procedures under subpart E of part 207.
§ 1271.26   When must I amend my establishment registration?
If the ownership or location of your establishment changes, or if there is a change in the United States agent's name, address, telephone number, or email address, you must submit an amendment to registration within 30 calendar days of the change.
§ 1271.27   Will FDA assign me a registration number?
(a) FDA will assign each location a permanent registration number.
(b) FDA acceptance of an establishment registration and HCT/P listing form does not constitute a determination that an establishment is in compliance with applicable rules and regulations or that the HCT/P is licensed or approved by FDA.
§ 1271.37   Will establishment registrations and HCT/P listings be available for inspection, and how do I request information on registrations and listings?
(a) Any registration on Form FDA 3356 filed in paper or electronic format by each establishment will be available for public inspection through the Center for Biologics Evaluation and Research Human Cell and Tissue Establishment Registration—Public Query Web site by using the CBER electronic Web-based application or by going in person to the Food and Drug Administration, Dockets Management Staff Public Reading Room (see address in § 20.120(a) of this chapter). The following information submitted under the HCT/P requirements is illustrative of the type of information that will be available for public disclosure when it is compiled:
(1) A list of all HCT/P's;
(2) A list of all HCT/P's manufactured by each establishment;
(3) A list of all HCT/P's discontinued; and
(4) All data or information that has already become a matter of public record.
(b) You should direct your other requests for information regarding HCT/P establishment registrations and HCT/P listings to the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Communication, Outreach and Development, 10903 New Hampshire Ave., Bldg. 71, Rm. 3103, Silver Spring, MD 20993-0002.
§ 1271.45   What requirements does this subpart contain?
(a) General. This subpart sets out requirements for determining donor eligibility, including donor screening and testing. The requirements contained in this subpart are a component of current good tissue practice (CGTP) requirements. Other CGTP requirements are set out in subpart D of this part.
(b) Donor-eligibility determination required. A donor-eligibility determination, based on donor screening and testing for relevant communicable disease agents and diseases, is required for all donors of cells or tissue used in HCT/Ps, except as provided under § 1271.90. In the case of an embryo or of cells derived from an embryo, a donor-eligibility determination is required for both the oocyte donor and the semen donor.
(c) Prohibition on use. An HCT/P must not be implanted, transplanted, infused, or transferred until the donor has been determined to be eligible, except as provided under §§ 1271.60(d), 1271.65(b), and 1271.90 of this subpart.
(d) Applicability of requirements. If you are an establishment that performs any function described in this subpart, you must comply with the requirements contained in this subpart that are applicable to that function.
§ 1271.47   What procedures must I establish and maintain?
(a) General. You must establish and maintain procedures for all steps that you perform in testing, screening, determining donor eligibility, and complying with all other requirements of this subpart. Establish and maintain means define, document (in writing or electronically), and implement; then follow, review, and as needed, revise on an ongoing basis. You must design these procedures to ensure compliance with the requirements of this subpart.
(b) Review and approval. Before implementation, a responsible person must review and approve all procedures.
(c) Availability. Procedures must be readily available to the personnel in the area where the operations to which they relate are performed, or in a nearby area if such availability is impractical.
(d) Departures from procedures. You must record and justify any departure from a procedure relevant to preventing risks of communicable disease transmission at the time of its occurrence. You must not make available for distribution any HCT/P from a donor whose eligibility is determined under such a departure unless a responsible person has determined that the departure does not increase the risks of communicable disease transmission through the use of the HCT/P.
(e) Standard procedures. You may adopt current standard procedures, such as those in a technical manual prepared by another organization, provided that you have verified that the procedures are consistent with and at least as stringent as the requirements of this part and appropriate for your operations.
§ 1271.50   How do I determine whether a donor is eligible?
(a) Determination based on screening and testing. If you are the establishment responsible for making the donor-eligibility determination, you must determine whether a donor is eligible based upon the results of donor screening in accordance with § 1271.75 and donor testing in accordance with §§ 1271.80 and 1271.85. A responsible person, as defined in § 1271.3(t), must determine and document the eligibility of a cell or tissue donor.
(b) Eligible donor. A donor is eligible under these provisions only if:
(1) Donor screening in accordance with § 1271.75 indicates that the donor:
(i) Is free from risk factors for, and clinical evidence of, infection due to relevant communicable disease agents and diseases; and
(ii) Is free from communicable disease risks associated with xenotransplantation; and
(2) The results of donor testing for relevant communicable disease agents in accordance with §§ 1271.80 and 1271.85 are negative or nonreactive, except as provided in § 1271.80(d)(1).
§ 1271.55   What records must accompany an HCT/P after the donor-eligibility determination is complete; and what records must I retain?
(a) Accompanying records. Once a donor-eligibility determination has been made, the following must accompany the HCT/P at all times:
(1) A distinct identification code affixed to the HCT/P container, e.g., alphanumeric, that relates the HCT/P to the donor and to all records pertaining to the HCT/P and, except in the case of autologous donations, directed reproductive donations, or donations made by first-degree or second-degree blood relatives, does not include an individual's name, social security number, or medical record number;
(2) A statement whether, based on the results of screening and testing, the donor has been determined to be eligible or ineligible; and
(3) A summary of the records used to make the donor-eligibility determination.
(b) Summary of records. The summary of records required by paragraph (a)(3) of this section must contain the following information:
(1) A statement that the communicable disease testing was performed by a laboratory:
(i) Certified to perform such testing on human specimens under the Clinical Laboratory Improvement Amendments of 1988 (42 U.S.C. 263a) and 42 CFR part 493; or
(ii) That has met equivalent requirements as determined by the Centers for Medicare and Medicaid Services in accordance with those provisions;
(2) A listing and interpretation of the results of all communicable disease tests performed;
(3) The name and address of the establishment that made the donor-eligibility determination; and
(4) In the case of an HCT/P from a donor who is ineligible based on screening and released under paragraph (b) of § 1271.65, a statement noting the reason(s) for the determination of ineligibility.
(c) Deletion of personal information. The accompanying records required by this section must not contain the donor's name or other personal information that might identify the donor.
(d) Record retention requirements. (1) You must maintain documentation of:
(i) Results and interpretation of all testing for relevant communicable disease agents in compliance with §§ 1271.80 and 1271.85, as well as the name and address of the testing laboratory or laboratories;
(ii) Results and interpretation of all donor screening for communicable diseases in compliance with § 1271.75; and
(iii) The donor-eligibility determination, including the name of the responsible person who made the determination and the date of the determination.
(2) All records must be accurate, indelible, and legible. Information on the identity and relevant medical records of the donor, as defined in § 1271.3(s), must be in English or, if in another language, must be retained and translated to English and accompanied by a statement of authenticity by the translator that specifically identifies the translated document.
(3) You must retain required records and make them available for authorized inspection by or upon request from FDA. Records that can be readily retrieved from another location by electronic means are considered “retained.”
(4) You must retain the records pertaining to a particular HCT/P at least 10 years after the date of its administration, or if the date of administration is not known, then at least 10 years after the date of the HCT/P's distribution, disposition, or expiration, whichever is latest.
§ 1271.60   What quarantine and other requirements apply before the donor-eligibility determination is complete?
(a) Quarantine. You must keep an HCT/P in quarantine, as defined in § 1271.3(q), until completion of the donor-eligibility determination required by § 1271.50. You must quarantine semen from anonymous donors until the retesting required under § 1271.85(d) is complete.
(b) Identification of HCT/Ps in quarantine. You must clearly identify as quarantined an HCT/P that is in quarantine pending completion of a donor-eligibility determination. The quarantined HCT/P must be easily distinguishable from HCT/Ps that are available for release and distribution.
(c) Shipping of HCT/Ps in quarantine. If you ship an HCT/P before completion of the donor-eligibility determination, you must keep it in quarantine during shipment. The HCT/P must be accompanied by records:
(1) Identifying the donor (e.g., by a distinct identification code affixed to the HCT/P container);
(2) Stating that the donor-eligibility determination has not been completed; and
(3) Stating that the product must not be implanted, transplanted, infused, or transferred until completion of the donor-eligibility determination, except under the terms of paragraph (d) of this section.
(d) Use in cases of urgent medical need. (1) This subpart C does not prohibit the implantation, transplantation, infusion, or transfer of an HCT/P from a donor for whom the donor-eligibility determination is not complete if there is a documented urgent medical need for the HCT/P, as defined in § 1271.3(u).
(2) If you make an HCT/P available for use under the provisions of paragraph (d)(1) of this section, you must prominently label it “NOT EVALUATED FOR INFECTIOUS SUBSTANCES,” and “ WARNING: Advise patient of communicable disease risks.” The following information must accompany the HCT/P:
(i) The results of any donor screening required under § 1271.75 that has been completed;
(ii) The results of any testing required under § 1271.80 or 1271.85 that has been completed; and
(iii) A list of any screening or testing required under § 1271.75, 1271.80 or 1271.85 that has not yet been completed.
(3) If you are the establishment that manufactured an HCT/P used under the provisions of paragraph (d)(1) of this section, you must document that you notified the physician using the HCT/P that the testing and screening were not complete.
(4) In the case of an HCT/P used for an urgent medical need under the provisions of paragraph (d)(1) of this section, you must complete the donor-eligibility determination during or after the use of the HCT/P, and you must inform the physician of the results of the determination.
§ 1271.65   How do I store an HCT/P from a donor determined to be ineligible, and what uses of the HCT/P are not prohibited?
(a) Storage. If you are the establishment that stores the HCT/P, you must store or identify HCT/Ps from donors who have been determined to be ineligible in a physically separate area clearly identified for such use, or follow other procedures, such as automated designation, that are adequate to prevent improper release until destruction or other disposition of the HCT/P in accordance with paragraph (b) or (c) of this section.
(b) Limited uses of HCT/P from ineligible donor. (1) An HCT/P from a donor who has been determined to be ineligible, based on the results of required testing and/or screening, is not prohibited by subpart C of this part from use for implantation, transplantation, infusion, or transfer under the following circumstances:
(i) The HCT/P is for allogeneic use in a first-degree or second-degree blood relative;
(ii) The HCT/P consists of reproductive cells or tissue from a directed reproductive donor, as defined in § 1271.3(l); or
(iii) There is a documented urgent medical need as defined in § 1271.3(u).
(2) You must prominently label an HCT/P made available for use under the provisions of paragraph (b)(1) of this section with the Biohazard legend shown in § 1271.3(h) with the statement “WARNING: Advise patient of communicable disease risks,” and, in the case of reactive test results, “WARNING: Reactive test results for (name of disease agent or disease).” The HCT/P must be accompanied by the records required under § 1271.55.
(3) If you are the establishment that manufactured an HCT/P used under the provisions of paragraph (b)(1) of this section, you must document that you notified the physician using the HCT/P of the results of testing and screening.
(c) Nonclinical use. You may make available for nonclinical purposes an HCT/P from a donor who has been determined to be ineligible, based on the results of required testing and/or screening, provided that it is labeled:
(1) “For Nonclinical Use Only” and
(2) With the Biohazard legend shown in § 1271.3(h).
§ 1271.75   How do I screen a donor?
(a) All donors. Except as provided under § 1271.90, if you are the establishment that performs donor screening, you must screen a donor of cells or tissue by reviewing the donor's relevant medical records for:
(1) Risk factors for, and clinical evidence of, relevant communicable disease agents and diseases, including:
(i) Human immunodeficiency virus;
(ii) Hepatitis B virus;
(iii) Hepatitis C virus;
(iv) Human transmissible spongiform encephalopathy, including Creutzfeldt-Jakob disease;
(v) Treponema pallidum ; and
(2) Communicable disease risks associated with xenotransplantation.
(b) Donors of viable, leukocyte-rich cells or tissue. In addition to the relevant communicable disease agents and diseases for which screening is required under paragraph (a) of this section, and except as provided under § 1271.90, you must screen the donor of viable, leukocyte-rich cells or tissue by reviewing the donor's relevant medical records for risk factors for and clinical evidence of relevant cell-associated communicable disease agents and diseases, including Human T-lymphotropic virus.
(c) Donors of reproductive cells or tissue. In addition to the relevant communicable disease agents and diseases for which screening is required under paragraphs (a) and (b) of this section, as applicable, and except as provided under § 1271.90, you must screen the donor of reproductive cells or tissue by reviewing the donor's relevant medical records for risk factors for and clinical evidence of infection due to relevant communicable diseases of the genitourinary tract. Such screening must include screening for the communicable disease agents listed in paragraphs (c)(1) and (c)(2) of this section. However, if the reproductive cells or tissues are recovered by a method that ensures freedom from contamination of the cells or tissue by infectious disease organisms that may be present in the genitourinary tract, then screening for the communicable disease agents listed in paragraphs (c)(1) and (c)(2) of this section is not required. Communicable disease agents of the genitourinary tract for which you must screen include:
(1) Chlamydia trachomatis ; and
(2) Neisseria gonorrhea.
(d) Ineligible donors. You must determine ineligible a donor who is identified as having either of the following:
(1) A risk factor for or clinical evidence of any of the relevant communicable disease agents or diseases for which screening is required under paragraphs (a)(1), (b), or (c) of this section; or
(2) Any communicable disease risk associated with xenotransplantation.
(e) Abbreviated procedure for repeat donors. If you have performed a complete donor screening procedure on a living donor within the previous 6 months, you may use an abbreviated donor screening procedure on repeat donations. The abbreviated procedure must determine and document any changes in the donor's medical history since the previous donation that would make the donor ineligible, including relevant social behavior.
§ 1271.80   What are the general requirements for donor testing?
(a) Testing for relevant communicable diseases is required. To adequately and appropriately reduce the risk of transmission of relevant communicable diseases, and except as provided under § 1271.90, if you are the establishment that performs donor testing, you must test a donor specimen for evidence of infection due to communicable disease agents in accordance with paragraph (c) of this section. You must test for those communicable disease agents specified in § 1271.85. In the case of a donor 1 month of age or younger, you must test a specimen from the birth mother instead of a specimen from the donor.
(b) Timing of specimen collection. You must collect the donor specimen for testing at the time of recovery of cells or tissue from the donor; or up to 7 days before or after recovery, except:
(1) For donors of peripheral blood stem/progenitor cells, bone marrow (if not excepted under § 1271.3(d)(4)), or oocytes, you may collect the donor specimen for testing up to 30 days before recovery; or
(2) In the case of a repeat semen donor from whom a specimen has already been collected and tested, and for whom retesting is required under § 1271.85(d), you are not required to collect a donor specimen at the time of each donation.
(c) Tests. You must test using appropriate FDA-licensed, approved, or cleared donor screening tests, in accordance with the manufacturer's instructions, to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents or diseases; however, until such time as appropriate FDA-licensed, approved, or cleared donor screening tests for Chlamydia trachomatis and for Neisseria gonorrhea are available, you must use FDA-licensed, approved, or cleared tests labeled for the detection of those organisms in an asymptomatic, low-prevalence population. You must use a test specifically labeled for cadaveric specimens instead of a more generally labeled test when applicable and when available. Required testing under this section must be performed by a laboratory that either is certified to perform such testing on human specimens under the Clinical Laboratory Improvement Amendments of 1988 (42 U.S.C. 263a) and 42 CFR part 493, or has met equivalent requirements as determined by the Centers for Medicare and Medicaid Services.
(d) Ineligible donors. You must determine the following donors to be ineligible:
(1) A donor whose specimen tests reactive on a screening test for a communicable disease agent in accordance with § 1271.85, except for a donor whose specimen tests reactive on a non-treponemal screening test for syphilis and negative on a specific treponemal confirmatory test;
(2)(i) A donor in whom plasma dilution sufficient to affect the results of communicable disease testing is suspected, unless:
(A) You test a specimen taken from the donor before transfusion or infusion and up to 7 days before recovery of cells or tissue; or
(B) You use an appropriate algorithm designed to evaluate volumes administered in the 48 hours before specimen collection, and the algorithm shows that plasma dilution sufficient to affect the results of communicable disease testing has not occurred.
(ii) Clinical situations in which you must suspect plasma dilution sufficient to affect the results of communicable disease testing include but are not limited to the following:
(A) Blood loss is known or suspected in a donor over 12 years of age, and the donor has received a transfusion or infusion of any of the following, alone or in combination:
( 1 ) More than 2,000 milliliters (mL) of blood (e.g., whole blood, red blood cells) or colloids within 48 hours before death or specimen collection, whichever occurred earlier, or
( 2 ) More than 2,000 mL of crystalloids within 1 hour before death or specimen collection, whichever occurred earlier.
(B) Regardless of the presence or absence of blood loss, the donor is 12 years of age or younger and has received a transfusion or infusion of any amount of any of the following, alone or in combination:
( 1 ) Blood (e.g., whole blood, red blood cells) or colloids within 48 hours before death or specimen collection, whichever occurred earlier, or
( 2 ) Crystalloids within 1 hour before death or specimen collection, whichever occurred earlier.
§ 1271.85   What donor testing is required for different types of cells and tissues?
(a) All donors. To adequately and appropriately reduce the risk of transmission of relevant communicable diseases, and except as provided under § 1271.90, you must test a specimen from the donor of cells or tissue, whether viable or nonviable, for evidence of infection due to relevant communicable disease agents, including:
(1) Human immunodeficiency virus, type 1;
(2) Human immunodeficiency virus, type 2;
(3) Hepatitis B virus;
(4) Hepatitis C virus; and
(5) Treponema pallidum.
(b) Donors of viable, leukocyte-rich cells or tissue. In addition to the relevant communicable disease agents for which testing is required under paragraph (a) of this section, and except as provided under § 1271.90,
(1) You must test a specimen from the donor of viable, leukocyte-rich cells or tissue to adequately and appropriately reduce the risk of transmission of relevant cell-associated communicable diseases, including:
(i) Human T-lymphotropic virus, type I; and
(ii) Human T-lymphotropic virus, type II.
(2) You must test a specimen from the donor of viable, leukocyte-rich cells or tissue for evidence of infection due to cytomegalovirus (CMV), to adequately and appropriately reduce the risk of transmission. You must establish and maintain a standard operating procedure governing the release of an HCT/P from a donor whose specimen tests reactive for CMV.
(c) Donors of reproductive cells or tissue. In addition to the communicable disease agents for which testing is required under paragraphs (a) and (b) of this section, as applicable, and except as provided under § 1271.90, you must test a specimen from the donor of reproductive cells or tissue to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents of the genitourinary tract. Such testing must include testing for the communicable disease agents listed in paragraphs (c)(1) and (c)(2) of this section. However, if the reproductive cells or tissues are recovered by a method that ensures freedom from contamination of the cells or tissue by infectious disease organisms that may be present in the genitourinary tract, then testing for the communicable disease agents listed in paragraphs (c)(1) and (c)(2) of this section is not required. Communicable disease agents of the genitourinary tract for which you must test include:
(1) Chlamydia trachomatis ; and
(2) Neisseria gonorrhea.
(d) Retesting anonymous semen donors. Except as provided under § 1271.90 and except for directed reproductive donors as defined in § 1271.3(l), at least 6 months after the date of donation of semen from anonymous donors, you must collect a new specimen from the donor and test it for evidence of infection due to the communicable disease agents for which testing is required under paragraphs (a), (b), and (c) of this section.
(e) Dura mater. For donors of dura mater, you must perform an adequate assessment designed to detect evidence of transmissible spongiform encephalopathy.
§ 1271.90   Are there other exceptions and what labeling requirements apply?
(a) Donor-eligibility determination not required. You are not required to make a donor-eligibility determination under § 1271.50 or to perform donor screening or testing under §§ 1271.75, 1271.80 and 1271.85 for:
(1) Cells and tissues for autologous use; or
(2) Reproductive cells or tissue donated by a sexually intimate partner of the recipient for reproductive use; or
(3) Cryopreserved cells or tissue for reproductive use, other than embryos, originally excepted under paragraphs (a)(1) or (a)(2) of this section at the time of donation, that are subsequently intended for directed donation, provided that:
(i) Additional donations are unavailable, for example, due to the infertility or health of a donor of the cryopreserved reproductive cells or tissue; and
(ii) Appropriate measures are taken to screen and test the donor(s) before transfer to the recipient.
(4) A cryopreserved embryo, originally excepted under paragraph (a)(2) of this section at the time of recovery or cryopreservation, that is subsequently intended for directed or anonymous donation. When possible, appropriate measures should be taken to screen and test the semen and oocyte donors before transfer of the embryo to the recipient.
(b) Exceptions for reproductive use. An embryo originally intended for reproductive use for a specific individual or couple that is subsequently intended for directed or anonymous donation for reproductive use is excepted from the prohibition on use under § 1271.45(c) even when the applicable donor eligibility requirements under subpart C of this part are not met. Nothing in this paragraph creates an exception for deficiencies that occurred in making the donor eligibility determination for either the oocyte donor or the semen donor as required under § 1271.45(b), or for deficiencies in performing donor screening or testing, as required under §§ 1271.75, 1271.80, and 1271.85.
(c) Required labeling. As applicable, you must prominently label an HCT/P described in paragraphs (a) and (b) of this section as follows:
(1) “FOR AUTOLOGOUS USE ONLY,” if it is stored for autologous use.
(2) “NOT EVALUATED FOR INFECTIOUS SUBSTANCES,” unless you have performed all otherwise applicable screening and testing under §§ 1271.75, 1271.80, and 1271.85. This paragraph does not apply to reproductive cells or tissue labeled in accordance with paragraph (c)(6) of this section.
(3) Unless the HCT/P is for autologous use only, “WARNING: Advise recipient of communicable disease risks,”
(i) When the donor-eligibility determination under § 1271.50(a) is not performed or is not completed; or
(ii) If the results of any screening or testing performed indicate:
(A) The presence of relevant communicable disease agents and/or
(B) Risk factors for or clinical evidence of relevant communicable disease agents or diseases.
(4) With the Biohazard legend shown in § 1271.3(h), if the results of any screening or testing performed indicate:
(i) The presence of relevant communicable disease agents and/or
(ii) Risk factors for or clinical evidence of relevant communicable disease agents or diseases.
(5) “WARNING: Reactive test results for (name of disease agent or disease),” in the case of reactive test results.
(6) “Advise recipient that screening and testing of the donor(s) were not performed at the time of recovery or cryopreservation of the reproductive cells or tissue, but have been performed subsequently,” for paragraphs (a)(3) or (a)(4) of this section.
§ 1271.145   Prevention of the introduction, transmission, or spread of communicable diseases.
You must recover, process, store, label, package, and distribute HCT/Ps, and screen and test cell and tissue donors, in a way that prevents the introduction, transmission, or spread of communicable diseases.
§ 1271.150   Current good tissue practice requirements.
(a) General. This subpart D and subpart C of this part set forth current good tissue practice (CGTP) requirements. You must follow CGTP requirements to prevent the introduction, transmission, or spread of communicable diseases by HCT/Ps (e.g., by ensuring that the HCT/Ps do not contain communicable disease agents, that they are not contaminated, and that they do not become contaminated during manufacturing). Communicable diseases include, but are not limited to, those transmitted by viruses, bacteria, fungi, parasites, and transmissible spongiform encephalopathy agents. CGTP requirements govern the methods used in, and the facilities and controls used for, the manufacture of HCT/Ps, including but not limited to all steps in recovery, donor screening, donor testing, processing, storage, labeling, packaging, and distribution. The CGTP provisions specifically governing determinations of donor eligibility, including donor screening and testing, are set out separately in subpart C of this part.
(b) Core CGTP requirements. The following are core CGTP requirements:
(1) Requirements relating to facilities in § 1271.190(a) and (b);
(2) Requirements relating to environmental control in § 1271.195(a);
(3) Requirements relating to equipment in § 1271.200(a);
(4) Requirements relating to supplies and reagents in § 1271.210(a) and (b);
(5) Requirements relating to recovery in § 1271.215;
(6) Requirements relating to processing and process controls in § 1271.220;
(7) Requirements relating to labeling controls in § 1271.250(a) and (b);
(8) Requirements relating to storage in § 1271.260 (a) through (d);
(9) Requirements relating to receipt, predistribution shipment, and distribution of an HCT/P in § 1271.265(a) through (d); and
(10) Requirements relating to donor eligibility determinations, donor screening, and donor testing in §§ 1271.50, 1271.75, 1271.80, and 1271.85.
(c) Compliance with applicable requirements —(1) Manufacturing arrangements (i) If you are an establishment that engages in only some operations subject to the regulations in this subpart and subpart C of this part, and not others, then you need only comply with those requirements applicable to the operations that you perform.
(ii) If you engage another establishment (e.g., a laboratory to perform communicable disease testing, or an irradiation facility to perform terminal sterilization), under a contract, agreement, or other arrangement, to perform any step in manufacture for you, that establishment is responsible for complying with requirements applicable to that manufacturing step.
(iii) Before entering into a contract, agreement, or other arrangement with another establishment to perform any step in manufacture for you, you must ensure that the establishment complies with applicable CGTP requirements. If, during the course of this contract, agreement, or other arrangement, you become aware of information suggesting that the establishment may no longer be in compliance with such requirements, you must take reasonable steps to ensure the establishment complies with those requirements. If you determine that the establishment is not in compliance with those requirements, you must terminate your contract, agreement, or other arrangement with the establishment.
(2) If you are the establishment that determines that an HCT/P meets all release criteria and makes the HCT/P available for distribution, whether or not you are the actual distributor, you are responsible for reviewing manufacturing and tracking records to determine that the HCT/P has been manufactured and tracked in compliance with the requirements of this subpart and subpart C of this part and any other applicable requirements.
(3) With the exception of §§ 1271.150(c) and 1271.155 of this subpart, the regulations in this subpart are not being implemented for reproductive HCT/Ps described in § 1271.10 and regulated solely under section 361 of the Public Health Service Act and the regulations in this part, or for the establishments that manufacture them.
(d) Compliance with parts 210, 211, and 820 of this chapter. With respect to HCT/Ps that are drugs (subject to review under an application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act or under a biological product license application under section 351 of the Public Health Service Act) or that are devices (subject to premarket review or notification under the device provisions of the act or under a biological product license application under section 351 of the Public Health Service Act), the procedures contained in this subpart and in subpart C of this part and the current good manufacturing practice regulations in parts 210 and 211 of this chapter and the quality system regulations in part 820 of this chapter supplement, and do not supersede, each other unless the regulations explicitly provide otherwise. In the event that a regulation in part 1271 of this chapter is in conflict with a requirement in parts 210, 211, or 820 of this chapter, the regulations more specifically applicable to the product in question will supersede the more general.
(e) Where appropriate. When a requirement is qualified by “where appropriate,” it is deemed to be “appropriate” unless you can document justification otherwise. A requirement is “appropriate” if nonimplementation of the requirement could reasonably be expected to result in the HCT/P not meeting its specified requirements related to prevention of introduction, transmission, or spread of communicable diseases, or in your inability to carry out any necessary corrective action.
§ 1271.155   Exemptions and alternatives.
(a) General. You may request an exemption from or alternative to any requirement in subpart C or D of this part.
(b) Request for exemption or alternative. Submit your request under this section to the Director of the appropriate Center (the Director), e.g., the Center for Biologics Evaluation and Research or the Center for Devices and Radiological Health. The request must be accompanied by supporting documentation, including all relevant valid scientific data, and must contain either:
(1) Information justifying the requested exemption from the requirement, or
(2) A description of a proposed alternative method of meeting the requirement.
(c) Criteria for granting an exemption or alternative. The Director may grant an exemption or alternative if he or she finds that such action is consistent with the goals of protecting the public health and/or preventing the introduction, transmission, or spread of communicable diseases and that:
(1) The information submitted justifies an exemption; or
(2) The proposed alternative satisfies the purpose of the requirement.
(d) Form of request. You must ordinarily make your request for an exemption or alternative in writing (hard copy or electronically). However, if circumstances make it difficult (e.g., there is inadequate time) to submit your request in writing, you may make the request orally, and the Director may orally grant an exemption or alternative. You must follow your oral request with an immediate written request, to which the Director will respond in writing.
(e) Operation under exemption or alternative. You must not begin operating under the terms of a requested exemption or alternative until the exemption or alternative has been granted. You may apply for an extension of an exemption or alternative beyond its expiration date, if any.
(f) Documentation. If you operate under the terms of an exemption or alternative, you must maintain documentation of:
(1) FDA's grant of the exemption or alternative, and
(2) The date on which you began operating under the terms of the exemption or alternative.
(g) Issuance of an exemption or alternative by the Director. In a public health emergency, the Director may issue an exemption from, or alternative to, any requirement in part 1271. The Director may issue an exemption or alternative under this section if the exemption or alternative is necessary to assure that certain HCT/Ps will be available in a specified location to respond to an unanticipated immediate need for those HCT/Ps.
§ 1271.160   Establishment and maintenance of a quality program.
(a) General. If you are an establishment that performs any step in the manufacture of HCT/Ps, you must establish and maintain a quality program intended to prevent the introduction, transmission, or spread of communicable diseases through the manufacture and use of HCT/Ps. The quality program must be appropriate for the specific HCT/Ps manufactured and the manufacturing steps performed. The quality program must address all core CGTP requirements listed in § 1271.150(b).
(b) Functions. Functions of the quality program must include:
(1) Establishing and maintaining appropriate procedures relating to core CGTP requirements, and ensuring compliance with the requirements of § 1271.180 with respect to such procedures, including review, approval, and revision;
(2) Ensuring that procedures exist for receiving, investigating, evaluating, and documenting information relating to core CGTP requirements, including complaints, and for sharing any information pertaining to the possible contamination of the HCT/P or the potential for transmission of a communicable disease by the HCT/P with the following:
(i) Other establishments that are known to have recovered HCT/Ps from the same donor;
(ii) Other establishments that are known to have performed manufacturing steps with respect to the same HCT/P; and
(iii) Relating to consignees, in the case of such information received after the HCT/P is made available for distribution, shipped to the consignee, or administered to the recipient, procedures must include provisions for assessing risk and appropriate followup, and evaluating the effect this information has on the HCT/P and for the notification of all entities to whom the affected HCT/P was distributed, the quarantine and recall of the HCT/P, and/or reporting to FDA, as necessary.
(3) Ensuring that appropriate corrective actions relating to core CGTP requirements, including reaudits of deficiencies, are taken and documented, as necessary. You must verify corrective actions to ensure that such actions are effective and are in compliance with CGTP. Where appropriate, corrective actions must include both short-term action to address the immediate problem and long-term action to prevent the problem's recurrence. Documentation of corrective actions must include, where appropriate:
(i) Identification of the HCT/P affected and a description of its disposition;
(ii) The nature of the problem requiring corrective action;
(iii) A description of the corrective action taken; and
(iv) The date(s) of the corrective action.
(4) Ensuring the proper training and education of personnel involved in activities related to core CGTP requirements;
(5) Establishing and maintaining appropriate monitoring systems as necessary to comply with the requirements of this subpart (e.g., environmental monitoring);
(6) Investigating and documenting HCT/P deviations and trends of HCT/P deviations relating to core CGTP requirements and making reports if required under § 1271.350(b) or other applicable regulations. Each investigation must include a review and evaluation of the HCT/P deviation, the efforts made to determine the cause, and the implementation of corrective action(s) to address the HCT/P deviation and prevent recurrence.
(c) Audits. You must periodically perform for management review a quality audit, as defined in § 1271.3(gg), of activities related to core CGTP requirements.
(d) Computers. You must validate the performance of computer software for the intended use, and the performance of any changes to that software for the intended use, if you rely upon the software to comply with core CGTP requirements and if the software either is custom software or is commercially available software that has been customized or programmed (including software programmed to perform a user defined calculation or table) to perform a function related to core CGTP requirements. You must verify the performance of all other software for the intended use if you rely upon it to comply with core CGTP requirements. You must approve and document these activities and results before implementation.
§ 1271.170   Personnel.
(a) General. You must have personnel sufficient to ensure compliance with the requirements of this part.
(b) Competent performance of functions. You must have personnel with the necessary education, experience, and training to ensure competent performance of their assigned functions. Personnel must perform only those activities for which they are qualified and authorized.
(c) Training. You must train all personnel, and retrain as necessary, to perform their assigned responsibilities adequately.
§ 1271.180   Procedures.
(a) General. You must establish and maintain procedures appropriate to meet core CGTP requirements for all steps that you perform in the manufacture of HCT/Ps. You must design these procedures to prevent circumstances that increase the risk of the introduction, transmission, or spread of communicable diseases through the use of HCT/Ps.
(b) Review and approval. Before implementation, a responsible person must review and approve these procedures.
(c) Availability. These procedures must be readily available to the personnel in the area where the operations to which they relate are performed, or in a nearby area if such availability is impractical.
(d) Standard procedures. If you adopt current standard procedures from another organization, you must verify that the procedures meet the requirements of this part and are appropriate for your operations.
§ 1271.190   Facilities.
(a) General. Any facility used in the manufacture of HCT/Ps must be of suitable size, construction, and location to prevent contamination of HCT/Ps with communicable disease agents and to ensure orderly handling of HCT/Ps without mix-ups. You must maintain the facility in a good state of repair. You must provide lighting, ventilation, plumbing, drainage, and access to sinks and toilets that are adequate to prevent the introduction, transmission, or spread of communicable disease.
(b) Facility cleaning and sanitation. (1) You must maintain any facility used in the manufacture of HCT/Ps in a clean, sanitary, and orderly manner, to prevent the introduction, transmission, or spread of communicable disease.
(2) You must dispose of sewage, trash, and other refuse in a timely, safe, and sanitary manner.
(c) Operations. You must divide a facility used in the manufacture of HCT/Ps into separate or defined areas of adequate size for each operation that takes place in the facility, or you must establish and maintain other control systems to prevent improper labeling, mix-ups, contamination, cross-contamination, and accidental exposure of HCT/Ps to communicable disease agents.
(d) Procedures and records. (1) You must establish and maintain procedures for facility cleaning and sanitation for the purpose of preventing the introduction, transmission, or spread of communicable disease. These procedures must assign responsibility for sanitation and must describe in sufficient detail the cleaning methods to be used and the schedule for cleaning the facility.
(2) You must document, and maintain records of, all cleaning and sanitation activities performed to prevent contamination of HCT/Ps. You must retain such records 3 years after their creation.
§ 1271.195   Environmental control and monitoring.
(a) Environmental control. Where environmental conditions could reasonably be expected to cause contamination or cross-contamination of HCT/Ps or equipment, or accidental exposure of HCT/Ps to communicable disease agents, you must adequately control environmental conditions and provide proper conditions for operations. Where appropriate, you must provide for the following control activities or systems:
(1) Temperature and humidity controls;
(2) Ventilation and air filtration;
(3) Cleaning and disinfecting of rooms and equipment to ensure aseptic processing operations; and
(4) Maintenance of equipment used to control conditions necessary for aseptic processing operations.
(b) Inspections. You must inspect each environmental control system periodically to verify that the system, including necessary equipment, is adequate and functioning properly. You must take appropriate corrective action as necessary.
(c) Environmental monitoring. You must monitor environmental conditions where environmental conditions could reasonably be expected to cause contamination or cross-contamination of HCT/Ps or equipment, or accidental exposure of HCT/Ps to communicable disease agents. Where appropriate, you must provide environmental monitoring for microorganisms.
(d) Records. You must document, and maintain records of, environmental control and monitoring activities.
§ 1271.200   Equipment.
(a) General. To prevent the introduction, transmission, or spread of communicable diseases, equipment used in the manufacture of HCT/Ps must be of appropriate design for its use and must be suitably located and installed to facilitate operations, including cleaning and maintenance. Any automated, mechanical, electronic, or other equipment used for inspection, measuring, or testing in accordance with this part must be capable of producing valid results. You must clean, sanitize, and maintain equipment according to established schedules.
(b) Procedures and schedules. You must establish and maintain procedures for cleaning, sanitizing, and maintaining equipment to prevent malfunctions, contamination or cross-contamination, accidental exposure of HCT/Ps to communicable disease agents, and other events that could reasonably be expected to result in the introduction, transmission, or spread of communicable diseases.
(c) Calibration of equipment. Where appropriate, you must routinely calibrate according to established procedures and schedules all automated, mechanical, electronic, or other equipment used for inspection, measuring, and testing in accordance with this part.
(d) Inspections. You must routinely inspect equipment for cleanliness, sanitation, and calibration, and to ensure adherence to applicable equipment maintenance schedules.
(e) Records. You must document and maintain records of all equipment maintenance, cleaning, sanitizing, calibration, and other activities performed in accordance with this section. You must display records of recent maintenance, cleaning, sanitizing, calibration, and other activities on or near each piece of equipment, or make the records readily available to the individuals responsible for performing these activities and to the personnel using the equipment. You must maintain records of the use of each piece of equipment, including the identification of each HCT/P manufactured with that equipment.
§ 1271.210   Supplies and reagents.
(a) Verification. You must not use supplies and reagents until they have been verified to meet specifications designed to prevent circumstances that increase the risk of the introduction, transmission, or spread of communicable diseases. Verification may be accomplished by the establishment that uses the supply or reagent, or by the vendor of the supply or reagent.
(b) Reagents. Reagents used in processing and preservation of HCT/Ps must be sterile, where appropriate.
(c) In-house reagents. You must validate and/or verify the processes used for production of in-house reagents.
(d) Records. You must maintain the following records pertaining to supplies and reagents:
(1) Records of the receipt of each supply or reagent, including the type, quantity, manufacturer, lot number, date of receipt, and expiration date;
(2) Records of the verification of each supply or reagent, including test results or, in the case of vendor verification, a certificate of analysis from the vendor; and
(3) Records of the lot of supply or reagent used in the manufacture of each HCT/P.
§ 1271.215   Recovery.
If you are an establishment that recovers HCT/Ps, you must recover each HCT/P in a way that does not cause contamination or cross-contamination during recovery, or otherwise increase the risk of the introduction, transmission, or spread of communicable disease through the use of the HCT/P.
§ 1271.220   Processing and process controls.
(a) General. If you are an establishment that processes HCT/Ps, you must process each HCT/P in a way that does not cause contamination or cross-contamination during processing, and that prevents the introduction, transmission, or spread of communicable disease through the use of the HCT/P.
(b) Pooling. Human cells or tissue from two or more donors must not be pooled (placed in physical contact or mixed in a single receptacle) during manufacturing.
(c) In-process control and testing. You must ensure that specified requirements, consistent with paragraph (a) of this section, for in-process controls are met, and that each in-process HCT/P is controlled until the required inspection and tests or other verification activities have been completed, or necessary approvals are received and documented. Sampling of in-process HCT/Ps must be representative of the material to be evaluated.
(d) Dura mater. (1) When there is a published validated process that reduces the risk of transmissible spongiform encephalopathy, you must use this process for dura mater (or an equivalent process that you have validated), unless following this process adversely affects the clinical utility of the dura mater.
(2) When you use a published validated process, you must verify such a process in your establishment.
§ 1271.225   Process changes.
Any change to a process must be verified or validated in accordance with § 1271.230, to ensure that the change does not create an adverse impact elsewhere in the operation, and must be approved before implementation by a responsible person with appropriate knowledge and background. You must communicate approved changes to the appropriate personnel in a timely manner.
§ 1271.230   Process validation.
(a) General. Where the results of processing described in § 1271.220 cannot be fully verified by subsequent inspection and tests, you must validate and approve the process according to established procedures. The validation activities and results must be documented, including the date and signature of the individual(s) approving the validation.
(b) Written representation. Any written representation that your processing methods reduce the risk of transmission of communicable disease by an HCT/P, including but not limited to, a representation of sterility or pathogen inactivation of an HCT/P, must be based on a fully verified or validated process.
(c) Changes. When changes to a validated process subject to paragraph (a) of this section occur, you must review and evaluate the process and perform revalidation where appropriate. You must document these activities.
§ 1271.250   Labeling controls.
(a) General. You must establish and maintain procedures to control the labeling of HCT/Ps. You must design these procedures to ensure proper HCT/P identification and to prevent mix-ups.
(b) Verification. Procedures must include verification of label accuracy, legibility, and integrity.
(c) Labeling requirements. Procedures must ensure that each HCT/P is labeled in accordance with all applicable labeling requirements, including those in §§ 1271.55, 1271.60, 1271.65, 1271.90, 1271.290, and 1271.370, and that each HCT/P made available for distribution is accompanied by documentation of the donor eligibility determination as required under § 1271.55.
§ 1271.260   Storage.
(a) Control of storage areas. You must control your storage areas and stock rooms to prevent:
(1) Mix-ups, contamination, and cross-contamination of HCT/Ps, supplies, and reagents, and
(2) An HCT/P from being improperly made available for distribution.
(b) Temperature. You must store HCT/Ps at an appropriate temperature.
(c) Expiration date. Where appropriate, you must assign an expiration date to each HCT/P based on the following factors:
(1) HCT/P type;
(2) Processing, including the method of preservation;
(3) Storage conditions; and
(4) Packaging.
(d) Corrective action. You must take and document corrective action whenever proper storage conditions are not met.
(e) Acceptable temperature limits. You must establish acceptable temperature limits for storage of HCT/Ps at each step of the manufacturing process to inhibit the growth of infectious agents. You must maintain and record storage temperatures for HCT/Ps. You must periodically review recorded temperatures to ensure that temperatures have been within acceptable limits.
§ 1271.265   Receipt, predistribution shipment, and distribution of an HCT/P.
(a) Receipt. You must evaluate each incoming HCT/P for the presence and significance of microorganisms and inspect for damage and contamination. You must determine whether to accept, reject, or place in quarantine each incoming HCT/P, based upon pre-established criteria designed to prevent communicable disease transmission.
(b) Predistribution shipment. If you ship an HCT/P within your establishment or between establishments (e.g., procurer to processor) and the HCT/P is not available for distribution as described in paragraph (c) of this section, you must first determine and document whether pre-established criteria designed to prevent communicable disease transmission have been met, and you must ship the HCT/P in quarantine.
(c) Availability for distribution. (1) Before making an HCT/P available for distribution, you must review manufacturing and tracking records pertaining to the HCT/P, and, on the basis of that record review, you must verify and document that the release criteria have been met. A responsible person must document and date the determination that an HCT/P is available for distribution.
(2) You must not make available for distribution an HCT/P that is in quarantine, is contaminated, is recovered from a donor who has been determined to be ineligible or for whom a donor-eligibility determination has not been completed (except as provided under §§ 1271.60, 1271.65, and 1271.90), or that otherwise does not meet release criteria designed to prevent communicable disease transmission.
(3) You must not make available for distribution any HCT/P manufactured under a departure from a procedure relevant to preventing risks of communicable disease transmission, unless a responsible person has determined that the departure does not increase the risk of communicable disease through the use of the HCT/P. You must record and justify any departure from a procedure at the time of its occurrence.
(d) Packaging and shipping. Packaging and shipping containers must be designed and constructed to protect the HCT/P from contamination. For each type of HCT/P, you must establish appropriate shipping conditions to be maintained during transit.
(e) Procedures. You must establish and maintain procedures, including release criteria, for the activities in paragraphs (a) through (d) of this section. You must document these activities. Documentation must include:
(1) Identification of the HCT/P and the establishment that supplied the HCT/P;
(2) Activities performed and the results of each activity;
(3) Date(s) of activity;
(4) Quantity of HCT/P subject to the activity; and
(5) Disposition of the HCT/P (e.g., identity of consignee).
(f) Return to inventory. You must establish and maintain procedures to determine if an HCT/P that is returned to your establishment is suitable to be returned to inventory.
§ 1271.270   Records.
(a) General. You must maintain records concurrently with the performance of each step required in this subpart and subpart C of this part. Any requirement in this part that an action be documented involves the creation of a record, which is subject to the requirements of this section. All records must be accurate, indelible, and legible. The records must identify the person performing the work and the dates of the various entries, and must be as detailed as necessary to provide a complete history of the work performed and to relate the records to the particular HCT/P involved.
(b) Records management system. You must establish and maintain a records management system relating to core CGTP requirements. Under this system, records pertaining to a particular HCT/P must be maintained in such a way as to facilitate review of the HCT/Ps history before making it available for distribution and, if necessary, subsequent to the HCT/Ps release as part of a followup evaluation or investigation. Records pertinent to the manufacture of HCT/Ps (e.g., labeling and packaging procedures, and equipment logs) must also be maintained and organized under the records management system. If records are maintained in more than one location, then the records management system must be designed to ensure prompt identification, location, and retrieval of all records.
(c) Methods of retention. You may maintain records required under this subpart electronically, as original paper records, or as true copies such as photocopies, microfiche, or microfilm. Equipment that is necessary to make the records available and legible, such as computer and reader equipment, must be readily available. Records stored in electronic systems must be backed up.
(d) Length of retention. You must retain all records for 10 years after their creation, unless stated otherwise in this part. However, you must retain the records pertaining to a particular HCT/P at least 10 years after the date of its administration, or if the date of administration is not known, then at least 10 years after the date of the HCT/Ps distribution, disposition, or expiration, whichever is latest. You must retain records for archived specimens of dura mater for 10 years after the appropriate disposition of the specimens.
(e) Contracts and agreements. You must maintain the name and address and a list of the responsibilities of any establishment that performs a manufacturing step for you. This information must be available during an inspection conducted under § 1271.400.
§ 1271.290   Tracking.
(a) General. If you perform any step in the manufacture of an HCT/P in which you handle the HCT/P, you must track each such HCT/P in accordance with this section, to facilitate the investigation of actual or suspected transmission of communicable disease and take appropriate and timely corrective action.
(b) System of HCT/P tracking. (1) You must establish and maintain a system of HCT/P tracking that enables the tracking of all HCT/Ps from:
(i) The donor to the consignee or final disposition; and
(ii) The consignee or final disposition to the donor.
(2) Alternatively, if you are an establishment that performs some but not all of the steps in the manufacture of an HCT/P in which you handle the HCT/P, you may participate in a system of HCT/P tracking established and maintained by another establishment responsible for other steps in the manufacture of the same HCT/P, provided that the tracking system complies with all the requirements of this section.
(c) Distinct identification code. As part of your tracking system, you must ensure: That each HCT/P that you manufacture is assigned and labeled with a distinct identification code, e.g., alphanumeric, that relates the HCT/P to the donor and to all records pertaining to the HCT/P; and that labeling includes information designed to facilitate effective tracking, using the distinct identification code, from the donor to the recipient and from the recipient to the donor. Except as described in § 1271.55(a)(1), you must create such a code specifically for tracking, and it may not include an individual's name, social security number, or medical record number. You may adopt a distinct identification code assigned by another establishment engaged in the manufacturing process, or you may assign a new code. If you assign a new code to an HCT/P, you must establish and maintain procedures for relating the new code to the old code.
(d) Tracking from consignee to donor. As part of your tracking system, you must establish and maintain a method for recording the distinct identification code and type of each HCT/P distributed to a consignee to enable tracking from the consignee to the donor.
(e) Tracking from donor to consignee or final disposition. As part of your tracking system, you must establish and maintain a method for documenting the disposition of each of your HCT/Ps, to enable tracking from the donor to the consignee or final disposition. The information you maintain must permit the prompt identification of the consignee of the HCT/P, if any.
(f) Consignees. At or before the time of distribution of an HCT/P to a consignee, you must inform the consignee in writing of the requirements in this section and of the tracking system that you have established and are maintaining to comply with these requirements.
(g) Requirements specific to dura mater donors. You must archive appropriate specimens from each donor of dura mater, under appropriate storage conditions, and for the appropriate duration, to enable testing of the archived material for evidence of transmissible spongiform encephalopathy, and to enable appropriate disposition of any affected nonadministered dura mater tissue, if necessary.
§ 1271.320   Complaint file.
(a) Procedures. You must establish and maintain procedures for the review, evaluation, and documentation of complaints as defined in § 1271.3(aa), relating to core current good tissue practice (CGTP) requirements, and the investigation of complaints as appropriate.
(b) Complaint file. You must maintain a record of complaints that you receive in a file designated for complaints. The complaint file must contain sufficient information about each complaint for proper review and evaluation of the complaint (including the distinct identification code of the HCT/P that is the subject of the complaint) and for determining whether the complaint is an isolated event or represents a trend. You must make the complaint file available for review and copying upon request from FDA.
(c) Review and evaluation of complaints. You must review and evaluate each complaint relating to core CGTP requirements to determine if the complaint is related to an HCT/P deviation or to an adverse reaction, and to determine if a report under § 1271.350 or another applicable regulation is required. As soon as practical, you must review, evaluate, and investigate each complaint that represents an event required to be reported to FDA, as described in § 1271.350. You must review and evaluate a complaint relating to core CGTP requirements that does not represent an event required to be reported to determine whether an investigation is necessary; an investigation may include referring a copy of the complaint to another establishment that performed manufacturing steps pertinent to the complaint. When no investigation is made, you must maintain a record that includes the reason no investigation was made, and the name of the individual(s) responsible for the decision not to investigate.
§ 1271.330   Applicability.
The provisions set forth in this subpart are being implemented for nonreproductive HCT/Ps described in § 1271.10 and regulated solely under section 361 of the Public Health Service Act and the regulations in this part, and for the establishments that manufacture those HCT/Ps. HCT/Ps that are drugs or devices regulated under the act, or are biological products regulated under section 351 of the Public Health Service Act, are not subject to the regulations set forth in this subpart.
§ 1271.350   Reporting.
(a) Adverse reaction reports. (1) You must investigate any adverse reaction involving a communicable disease related to an HCT/P that you made available for distribution. You must report to FDA an adverse reaction involving a communicable disease if it:
(i) Is fatal;
(ii) Is life-threatening;
(iii) Results in permanent impairment of a body function or permanent damage to body structure; or
(iv) Necessitates medical or surgical intervention, including hospitalization.
(2) You must submit each report on a Form FDA-3500A to the address in paragraph (a)(5) of this section within 15 calendar days of initial receipt of the information.
(3) You must, as soon as practical, investigate all adverse reactions that are the subject of these 15-day reports and must submit followup reports within 15 calendar days of the receipt of new information or as requested by FDA. If additional information is not obtainable, a followup report may be required that describes briefly the steps taken to seek additional information and the reasons why it could not be obtained.
(4) You may obtain copies of the reporting form (FDA-3500A) from the Center for Biologics Evaluation and Research (see address in paragraph (a)(5) of this section). Electronic Form FDA-3500A may be obtained at http://www.fda.gov/medwatch or at http://www.hhs.gov/forms.
(5) You must submit two copies of each report described in this paragraph to the Food and Drug Administration, Center for Biologics Evaluation and Research, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G112, Silver Spring, MD 20993-0002. FDA may waive the requirement for the second copy in appropriate circumstances.
(b) Reports of HCT/P deviations. (1) You must investigate all HCT/P deviations related to a distributed HCT/P for which you performed a manufacturing step.
(2) You must report any such HCT/P deviation relating to the core CGTP requirements, if the HCT/P deviation occurred in your facility or in a facility that performed a manufacturing step for you under contract, agreement, or other arrangement. Each report must contain a description of the HCT/P deviation, information relevant to the event and the manufacture of the HCT/P involved, and information on all follow-up actions that have been or will be taken in response to the HCT/P deviation (e.g., recalls).
(3) You must report each such HCT/P deviation that relates to a core CGTP requirement on Form FDA 3486 within 45 days of the discovery of the event either electronically using the Center for Biologics Evaluation and Research electronic Web-based application or by mail to the Food and Drug Administration, Center for Biologics Evaluation and Research, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G112, Silver Spring, MD 20993-0002.
§ 1271.370   Labeling.
The following requirements apply in addition to §§ 1271.55, 1271.60, 1271.65, and 1271.90:
(a) You must label each HCT/P made available for distribution clearly and accurately.
(b) The following information must appear on the HCT/P label:
(1) Distinct identification code affixed to the HCT/P container, and assigned in accordance with § 1271.290(c);
(2) Description of the type of HCT/P;
(3) Expiration date, if any; and
(4) Warnings required under § 1271.60(d)(2), § 1271.65(b)(2), or § 1271.90(c), if applicable and physically possible. If it is not physically possible to include these warnings on the label, the warnings must, instead, accompany the HCT/P.
(c) The following information must either appear on the HCT/P label or accompany the HCT/P:
(1) Name and address of the establishment that determines that the HCT/P meets release criteria and makes the HCT/P available for distribution;
(2) Storage temperature;
(3) Other warnings, where appropriate; and
(4) Instructions for use when related to the prevention of the introduction, transmission, or spread of communicable diseases.
§ 1271.390   Applicability.
The provisions set forth in this subpart are applicable only to HCT/Ps described in § 1271.10 and regulated solely under section 361 of the Public Health Service Act and the regulations in this part, and to the establishments that manufacture those HCT/Ps. HCT/Ps that are drugs or devices regulated under the act, or are biological products regulated under section 351 of the Public Health Service Act, are not subject to the regulations set forth in this subpart.
§ 1271.400   Inspections.
(a) If you are an establishment that manufactures HCT/Ps described in § 1271.10, whether or not under contract, you must permit the Food and Drug Administration (FDA) to inspect any manufacturing location at any reasonable time and in a reasonable manner to determine compliance with applicable provisions of this part. The inspection will be conducted as necessary in the judgment of the FDA and may include your establishment, facilities, equipment, finished and unfinished materials, containers, processes, HCT/Ps, procedures, labeling, records, files, papers, and controls required to be maintained under the part. The inspection may be made with or without prior notification and will ordinarily be made during regular business hours.
(b) The frequency of inspection will be at the agency's discretion.
(c) FDA will call upon the most responsible person available at the time of the inspection of the establishment and may question the personnel of the establishment as necessary to determine compliance with the provisions of this part.
(d) FDA's representatives may take samples, may review and copy any records required to be kept under this part, and may use other appropriate means to record evidence of observations during inspections conducted under this subpart.
(e) The public disclosure of records containing the name or other positive identification of donors or recipients of HCT/Ps will be handled in accordance with FDA's procedures on disclosure of information as set forth in parts 20 and 21 of this chapter.
§ 1271.420   HCT/Ps offered for import.
(a) Except as provided in paragraphs (c) and (d) of this section, when an HCT/P is offered for import, the importer of record must notify, either before or at the time of importation, the director of the district of the Food and Drug Administration (FDA) having jurisdiction over the port of entry through which the HCT/P is imported or offered for import, or such officer of the district as the director may designate to act in his or her behalf in administering and enforcing this part, and must provide sufficient information, including information submitted in the Automated Commercial Environment (ACE) system or any other electronic data interchange system authorized by the U.S. Customs and Border Protection Agency as required in part 1, subpart D of this chapter, for FDA to make an admissibility decision.
(b) Except as provided in paragraphs (c) and (d) of this section, an HCT/P offered for import must be held intact by the importer or consignee, under conditions necessary to prevent transmission of communicable disease, until an admissibility decision is made by FDA. The HCT/P may be transported under quarantine to the consignee, while the FDA district reviews the documentation accompanying the HCT/P. When FDA makes a decision regarding the admissibility of the HCT/P, FDA will notify the importer of record.
(c) This section does not apply to reproductive HCT/Ps regulated solely under section 361 of the Public Health Service Act and the regulations in this part, and donated by a sexually intimate partner of the recipient for reproductive use.
(d) This section does not apply to peripheral blood stem/progenitor cells regulated solely under section 361 of the Public Health Service Act and the regulations in this part, except that paragraphs (a) and (b) of this section apply when circumstances occur under which such imported peripheral blood stem/progenitor cells may present an unreasonable risk of communicable disease transmission which indicates the need to review the information referenced in paragraph (a) of this section.
§ 1271.440   Orders of retention, recall, destruction, and cessation of manufacturing.
(a) Upon an agency finding that there are reasonable grounds to believe that an HCT/P is a violative HCT/P because it was manufactured in violation of the regulations in this part and, therefore, the conditions of manufacture of the HCT/P do not provide adequate protections against risks of communicable disease transmission; or the HCT/P is infected or contaminated so as to be a source of dangerous infection to humans; or an establishment is in violation of the regulations in this part and, therefore, does not provide adequate protections against the risks of communicable disease transmission, the Food and Drug Administration (FDA) may take one or more of the following actions:
(1) Serve upon the person who distributed the HCT/P a written order that the HCT/P be recalled and/or destroyed, as appropriate, and upon persons in possession of the HCT/P that the HCT/P must be retained until it is recalled by the distributor, destroyed, or disposed of as agreed by FDA, or the safety of the HCT/P is confirmed;
(2) Take possession of and/or destroy the violative HCT/P; or
(3) Serve upon the establishment an order to cease manufacturing until compliance with the regulations of this part has been achieved. When FDA determines there are reasonable grounds to believe there is a danger to health, such order will be effective immediately. In other situations, such order will be effective after one of the following events, whichever is later:
(i) Passage of 5 working days from the establishment's receipt of the order; or
(ii) If the establishment requests a hearing in accordance with paragraph (e) of this section and part 16 of this chapter, a decision in, and in accordance with, those proceedings.
(b) A written order issued under paragraph (a) of this section will state with particularity the facts that justify the order.
(c)(1) A written order issued under paragraph (a)(1) of this section will ordinarily provide that the HCT/P be recalled and/or destroyed within 5 working days from the date of receipt of the order. After receipt of an order issued under paragraph (a)(1) of this section, the establishment in possession of the HCT/P must not distribute or dispose of the HCT/P in any manner except to recall and/or destroy the HCT/P consistent with the provisions of the order, under the supervision of FDA.
(2) In lieu of paragraph (c)(1) of this section, other arrangements for assuring the proper disposition of the HCT/P may be agreed upon by the person receiving the written order and FDA. Such arrangements may include, among others, providing FDA with records or other written information that adequately ensure that the HCT/P has been recovered, processed, stored, and distributed in conformance with this part, and that, except as provided under §§ 1271.60, 1271.65, and 1271.90, the donor of the cells or tissue for the HCT/P has been determined to be eligible.
(d) A written order issued under paragraph (a)(3) of this section will specify the regulations with which you must achieve compliance and will ordinarily specify the particular operations covered by the order. After receipt of an order that is in effect and issued under paragraph (a)(3) of this section, you must not resume operations without prior written authorization of FDA.
(e) The recipient of an order issued under this section may request a hearing in accordance with part 16 of this chapter. To request a hearing, the recipient of the written order or prior possessor of such HCT/P must make the request within 5 working days of receipt of a written order for retention, recall, destruction, and/or cessation (or within 5 working days of the agency's possession of an HCT/P under paragraph (a)(2) of this section), in accordance with part 16 of this chapter. An order of destruction will be held in abeyance pending resolution of the hearing request. Upon request under part 16 of this chapter, FDA will provide an opportunity for an expedited hearing for an order of cessation that is not stayed by the Commissioner of Food and Drugs.
(f) FDA will not issue an order for the destruction of reproductive tissue under paragraph (a)(1) of this section, nor will it carry out such destruction itself under paragraph (a)(2) of this section.