Good Tissue Practice (CGTP) Final Rule Questions and Answers
What is the purpose of the current good tissue practice rule?
FDA finalized its proposed requirements for current good tissue practice for establishments that manufacture human cell, tissue, and cellular and tissue-based products (HCT/Ps). FDA believes that, together with establishment registration, HCT/P listing, donor screening and donor testing requirements, requirements for current good tissue practice will increase the safety of HCT/Ps, and public confidence in their safety, by preventing the introduction, transmission and spread of communicable disease. The agency's actions are intended to improve protection of the public health while minimizing regulatory burden.
When did the current good tissue practice final rule become effective?
The good tissue practice rule became effective on May 25, 2005.
What regulatory changes occurred on May 25, 2005?
Human heart valve allografts and human dura mater allografts were previously regulated as medical devices. Human heart valve allografts and human dura mater allografts are now regulated solely as HCT/Ps under section 361 of the Public Health Service Act assuming they meet the criteria in section 1271.10(a). The January 27, 2004 Interim Final Rule, which previously regulated these products as medical devices, has been revoked.
Do the requirements in the current good tissue practice rule apply to HCT/Ps recovered before the effective date?
The requirements apply to HCT/Ps recovered on or after the effective date. We have amended part 1270 by modifying the definition of human tissue intended for transplantation [1270.3(j)] to limit its applicability to tissue collected before May 25, 2005.
Did FDA already have requirements for current good tissue practice prior to the effective date of this rule?
Although FDA previously regulated human tissue intended for transplantation (e.g., musculoskeletal, skin, and ocular tissues) under 21 CFR part 1270, this rule represents FDA’s first list of comprehensive good tissue practice requirements for HCT/P establishments. Part 1270 contains requirements for determining the suitability of a donor of human tissue intended for transplantation, as well as requirements for written procedures, (including written procedures that have been prepared, validated, and followed for prevention of infectious disease contamination and cross-contamination by tissue during processing), record keeping, and inspection. The CGTP final rule is codified in 21 CFR part 1271, subparts D, E, and F.
Do the requirements in subparts D and E of the current good tissue practice rule apply to reproductive HCT/Ps?
With the exception of 21 CFR 1271.150(c) and 1271.155, the regulations in subpart D are not being implemented for reproductive HCT/Ps described in 1271.10 and regulated solely under section 361 of the PHS Act. The regulations in subpart E are implemented for nonreproductive HCT/Ps only, therefore the regulations for adverse reaction and HCT/P deviation reporting, and for labeling do not apply to reproductive HCT/Ps.
We received comments to the docket questioning application of some of the good tissue practice requirements to reproductive HCT/Ps. Although there have been few recent reports of transmission of communicable disease via reproductive HCT/Ps, we don't know whether this is because such HCT/Ps pose low risk or whether occurrences of disease transmission are overlooked or under-reported. Additional information on the scope of risk and appropriate measures to reduce risk will help us assess the need for extending good tissue practice requirements to reproductive HCT/Ps in the future.
What is current good tissue practice?
Current good tissue practice are the requirements in subparts C and D of 21 CFR part 1271 that 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.
What is the purpose of the current good tissue practice requirements?
The requirements aim to prevent the introduction, transmission, and spread of communicable diseases by HCT/Ps, by ensuring that the HCT/Ps do not contain communicable disease agents, they are not contaminated, and they do not become contaminated during manufacturing.
If an establishment only performs certain activities in the manufacture of HCT/Ps, does the establishment need to follow all current good tissue practice requirements?
An establishment need only comply with those requirements applicable to the operations that it performs. For instance, a laboratory that performs communicable disease testing but does not store HCT/Ps would not have to meet the requirements for HCT/P storage.
What are the functions of a quality program with regard to HCT/Ps?
The quality program must ensure that procedures relating to core good tissue practices requirements are established and maintained. The quality program must have procedures for receiving, investigating, evaluating and documenting information relating to core good tissue practices, including complaints, and for sharing any information about contamination, potential contamination, or potential communicable disease transmission with other establishments. Also, the quality program must ensure that corrective and preventive actions relating to core current good tissue practice are taken and documented and that HCT/P deviations related to core requirements are investigated and trended. The quality program must have an auditing system in place to periodically perform, for management review, a quality audit related to core requirements.
Do the current good tissue practice regulations require any specific procedures that must be followed during recovery?
The regulations require that you recover each HCT/P in a way that does not cause contamination or cross-contamination during recovery, or otherwise increase the risk of introduction, transmission, or spread of communicable disease through the use of the HCT/P (21 CFR 1271.215). We expect to develop guidance in the future that provides more specific information on procedures for recovery.
Is pooling of HCT/Ps prohibited?
HCT/Ps from two or more donors must not be pooled (placed in physical contact or mixed in a single container) during manufacturing. We clarified in the preamble that this does not prohibit the administration of several products sequentially. Establishments may request an exemption or alternative to this requirement provided that data are submitted to show that the benefits of pooling outweigh the risks, in a particular case.
What happens when a change is made to a process in tissue manufacturing?
Any change to a process must be verified or validated to ensure the change does not create an adverse impact elsewhere in the operation. Any change to a process must be approved before implementation by a responsible person with appropriate knowledge and background. In addition, approved changes must be communicated to the appropriate personnel in a timely manner (21 CFR 1271.225).
Does FDA require that HCT/Ps be sterile?
As technology progresses, it may be possible to manufacture sterile HCT/Ps and/or inactivate pathogens. Any written representation that an establishment's processing methods reduce the risk of transmission of communicable diseases by an HCT/P, including a representation of sterility or pathogen inactivation, must be based on a fully verified or validated process [21 CFR 1271.230 (b)].
What does an FDA inspection of an HCT/P establishment involve?
An FDA inspection will be conducted to determine compliance with the applicable provisions in 21 CFR Part 1271. The FDA inspection may include, but is not limited to, an assessment of the establishment's facilities, equipment, finished and unfinished materials, containers, processes, HCT/Ps, procedures, labeling, records, files, papers, and controls required to be maintained under the regulations. FDA representatives may review and copy any records required to be kept under 21 CFR part 1271. Financial records and personnel records are not required records under part 1271. For reproductive establishments, inspection will be limited to determining compliance with the applicable provisions contained in subparts A, B, C, and sections 1271.150(c) and 1271.155 in subpart D.
Are FDA HCT/P establishment inspections conducted during regular business hours?
An FDA inspection will ordinarily be performed during regular business hours and may be made with or without prior notification. The frequency of inspections will be at the Agency's discretion.
What enforcement provisions are included in the regulations in order to prevent the introduction, transmission, or spread of communicable diseases?
As provided in the final rule, FDA may issue orders of retention, recall, destruction, or cessation of manufacturing.
When would FDA issue an order for retention, recall, or destruction for HCT/Ps?
FDA may issue an order for retention, recall or destruction of HCT/Ps upon an Agency finding that there are reasonable grounds to believe that an HCT/P is violative because it was manufactured in violation of the regulations and, therefore, the conditions of manufacture 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; or an establishment is in violation of the regulations and therefore, does not provide adequate protections against the risks of communicable disease transmission.