AABB细胞治疗产品标准[第四版] (1)

1、Proposed Standards for Cellular Therapy Standards, 4th editionIntroductionThe Cellular Therapy Standards Program Unit is soliciting public comment on the proposed Standards for Cellular Therapy Product Services, 4th edition. The summary below presents the most important changes to the proposed CT St

2、andards, 4th edition. Many of the changes are best understood when reviewed in the context of the document. These changes are marked here to assist in your review, but please note that the actual CT Standards is presented without marked changes.To submit comments:1. Send comments by July 29, 2009 to

3、 the Standards Development Department, AABB National Office, 8101 Glenbrook Road, Bethesda, MD 20814; fax (301) 657-0957; email: .2. Include name and postal address/fax number/email address, as appropriate.3. Identify the standard by its number at the beginning of the comments. This

4、 identification is especially helpful if you comment on more than one standard.4. Provide alternative wording if you think it would improve the clarity of a standard. If you agree or disagree strongly with a proposed change, please state your reasons or submit data.Significant Changes to the Propose

5、d Standards1.1.2Executive ManagementThe facility shall define executive management. Executive management shall have responsibility and authority for the facilitys operations, for appointing a management quality representative, and for performing management reviews. Executive management shall have th

6、e authority to establish or make changes to the facilitys quality and operational policies, processes, and procedures.The CT SPU elected to clarify this standard. The change addresses confusion about whether the “management representative” and “quality representative” can be the same individual. Not

7、e that the term “quality representative is also used later in the section.!C 2.2.3 CompetenceEvaluations of competence shall be performed before independent performance of assigned activities and annually thereafter for definedPROPOSED Standards for Cellular Therapy Product Services, 4th edition1Dra

8、ft for comment purposes onlyComment period: May 29 July 29, 2009tasks and activities.*42 CFR 493.1451(b)(8).The clause “for defined tasks and activities” is new. The new language is intended to capture the fact that initial competence may be a broad evaluation, but that ongoing competence is necessa

9、ry for specific tasks and activities related to the individuals position.Calibration and Accuracy of EquipmentThe facility shall:1) Identify equipment that requires calibration so that the calibration status can be determined.The CT SPU elected to remove this clause, reasoning that the delete

10、d language amounted to guidance rather than a requirement.3.1.2Computer SystemsImplementation and modification of computer system software, hardware, and databases shall be planned and controlled. Elements of planning and control shall include:1) Designation of system versions with inclusive dates o

11、f use.2) Validation/verification of system software, hardware, databases, and user-defined tables.3) Fulfillment of life-cycle requirements for internally developed software.4) Defined processes for system operation and maintenance.5) Defined process for authorizing and documenting modifications to

12、the system.6) System security to prevent unauthorized access.7) Documentation that is understandable to the user.8) Functionality that allows for display and verification of data before final acceptance of the additions or alterations.9) Defined process for monitoring of data integrity for critical

13、data elementsAlternative SystemsThe facility shall have alternative systems to ensure accessto critical information and continuous operation ofcritical activities in the event that electronic data andcomputer-assisted functions are not available..1The alternative systems shall be teste

14、dperiodically.PROPOSED Standards for Cellular Therapy Product Services, 4th edition2Draft for comment purposes onlyComment period: May 29 July 29, 2009The standards above have been updated to reflect current practices regarding the use of computer systems.!F International Shipment of Cellular

15、 Therapy Products(NEW STANDARD)Before international shipment of cellular therapy products, thereshall be an agreement between the donor/product registry orshipping facility and the receiving facility, describing eachfacilitys responsibility with regard to meeting applicable local ornational regulati

16、ons. The agreement shall include provisions forthe sharing of documentation required to meet each countrysimport/export regulatory requirements.Standard is new to the proposed edition of CT Standards. The requirement reflects the awareness on the part of the CT SPU that chain of supply for a

17、 cellular therapy product can extend beyond national boundaries. A number of other standards address this issue as well.4.2.3Qualification of Facilities Providing Cellular Therapy ProductsNEW STANDARDFacilities purchasing or receiving products from other facilities shall have policies, processes and

18、 procedures that address the accreditation status of the facility providing the product.See also 5.10.7 below.5.3Process Development and ChangeNEW STANDARDThe development of new processes and procedures or changes to existing ones shall be controlled.5.3.1Process PlanningNEW STANDARDQuality requirem

19、ents shall be incorporated into the development of new or changed products or services. Standards 4.1 and 5.1 apply. Planning and implementation activities at a minimum shall include the following:1) Evaluation of accreditation, regulatory and legal requirements related to the new or changed process

20、, product or service.2) Review of current available knowledge (e.g., other successful practices, nonconformances).3) Evaluation of risk.4) Identification of affected parties and mechanism to communicate relevant information5) Identification of performance measures as applicable to the new or changed

21、 process, product or service.6) Evaluation of resource requirements.PROPOSED Standards for Cellular Therapy Product Services, 4th edition3Draft for comment purposes onlyComment period: May 29 July 29, 20097) Evaluation of the impact of the new or changed process, product or service on other facility

22、 or program processes.8) Evaluation of the need to create or revise documents for the new or changed process, product or service.9) Validation of new or changed processes and procedures (including those affecting equipment use) before implementation. Standard 6.2.3 applies.10) Implementation plan.11

23、) Postimplementation evaluations.5.3.2Novel MethodsNEW STANDARDThe facility shall control the design and implementation of novel methods or practices to ensure that specified requirements are met. Implementation of novel methods or practices shall include:1) Identification of goals, expected outcome

24、s, and/or performance measures.2) Review of existing accreditation, regulatory, and legal requirements to identify potential conflicts.3) Criteria for review of outcomes.4) Review of actual results.5) Actions to be taken if goals are not met.6) Implementation plan.7) Validation8) Postimplementation

25、evaluations.This section has been revised with the goal of clarifying the intent of design control by distinguishing between routine change control and the need for controlled innovation in the cellular therapy arena. The CT SPU expanded the language surrounding routine change control intended to ca

26、pture the implementation of a process or procedure that is widely used but which is new to the facility. Novel methods, on the other hand, are innovative practices that are not widely used in the field or which may not be peer-reviewed.The CT SPU elected to define a “novel method” as follows:Novel M

27、ethod: An innovative method or procedure being evaluated and introduced into practice at a facility. The method may not have undergone internal or external peer review or approval by institutional review board.The CT SPU is requesting specific feedback over whether this proposed revision represents

28、an improvement over the previous wording.5.10.7Donor Eligibility and Testing for International Cellular Therapy ProductsNEW STANDARDPROPOSED Standards for Cellular Therapy Product Services, 4th edition4Draft for comment purposes onlyComment period: May 29 July 29, 2009Before international shipment o

29、f cellular therapy products the receiving facility shall review the donor eligibility and infectious disease testing records of the donor for compliance with applicable local or national regulations of the receiving facility.This standard is new to this edition of the proposed Standards. It addresse

30、s the challenge of obtaining cellular therapy products that were procured outside of the receiving country.!FAbnormal results on the donor medical history screening or testingthat may affect the recipients health or the therapeutic value of thecellular therapy product shall be communicated t

31、o the recipientsphysician before distributionreleaseof the cellular therapyproduct for clinical use, in conformance with Reference StandardA, Requirements for Notification of Abnormal Results,and Standard 7.1.The CT SPU changed the term “release” to “distribution” throughout the document. Th

32、is change has been made throughout the proposed standards as well, where appropriate. Note the definitions of the two terms presented below.Distribution: The act of transferring a cellular therapy product that meets applicable product release criteria specified requirements from 1) a location of pro

33、cessing/manufacture or 2) an intermediate separate holding location for storage to either the location of medical administration or another intermediate separate holding location for temporary storage before infusion. (Such transfer may be within a facility, institution, or organization or between d

34、ifferent facilities. Accordingly, distribution may involve transportation of the product over significant distances and may include commercial shipping or travel with a courier, outside the direct control of both distributing and receiving facilities.)Release: Removal of a product from quarantine or

35、 in-process status for the purpose of distribution.! F5.15 Transportion and ShippingThe facility shall establish and maintain policies, processes, and procedures that are intended to limit deterioration, prevent damage, ensure timely delivery, and protect the quality of the materials and cellular th

36、erapy products during transport and shipping.5.15.1The facility shall control packaging to the extent necessary to ensure conformance with specified requirements. Local, federal national, and/or international transportion/shipping regulations apply.!C5.15.2ShippingContainers shall be qualified at de

37、fined intervals to ensure thatthey maintain temperatures within the acceptable range for the expectedPROPOSED Standards for Cellular Therapy Product Services, 4th edition5Draft for comment purposes onlyComment period: May 29 July 29, 2009duration of transportionor shipping.!F5.15.3 Whennoncryopreser

38、vedproducts are transported or shippedbetween orwithin facilities, the extent of temperature monitoring shall be definedand shall be appropriate to the duration of transportionor shipping.!FWhen cryopreserved products are shippedtransported andare beyond the physical control of the facility,

39、 thetemperature of the shipping container shall be continuouslymonitored.If the cellular therapy product remains underthe physical control of the facility, the extent of monitoringshall be defined.5.15.4The facility shall label shipping containers and cellular therapy productsin a manner designed to

40、 allow positive identification and toalertinformthe carrier of the appropriate handling. Reference Standards 5.9.1A,Requirements for Labeling of Cellular Therapy Products,and5.9.1B,Biohazard and Warning Labels, and 5.9.1C, Requirements for LabelingShipping Containers apply.5.15.5 Product inserts and

41、 records shall accompany products being shipped asdefined in policies, processes, and procedures. Reference Standard5.15.5A, Labeling and Packaging Requirements Upon Shipping ofCellular Therapy Products, applies.Standards 5.15 5.15.5 have been edited, though the intent is largely unchanged.Previousl

42、y, the body of the standard discussed whether a product is under the control ofqualified staff or not during transportation or shipping. This concept is now addressed inthe glossary (see below.) The term “shipping” is now defined as follows:Shipping: The physical act of transferring a cellular thera

43、py product within or betweenfacilities. During shipping the product leaves the control of trained personnel at theoriginating or receiving facility.By contrast, “transport” is defined as follows:Transport: The physical act of transferring a cellular therapy product within or betweenfacilities. Durin

44、g transport the product does not leave the control of trained personnel atthe originating or receiving facility.!F5.17.1 Processing RecordA complete processing record shall include:1)Unique donation identifier.2)Additional unique product identifiers used during processing,preservation, and storage s

45、teps.3)Name and address of processing facility.PROPOSED Standards for Cellular Therapy Product Services, 4th edition6Draft for comment purposes onlyComment period: May 29 July 29, 20094) All pertinent details of critical processing, preservation, and storage steps. For cryopreservation records, stan

46、dard applies.5) Date and time (if applicable) of critical steps.6) Names of persons responsible for each step.7) Names, manufacturers, lot numbers, and expiration dates of all critical materials used in processing, preservation, and storage.8) Quantities of reagents used.9) Identifiers of e

47、quipment used.10) Documentation of product distribution or final disposition.11) Final review as defined by the facilitys quality plan.Sub number 4 was revised to further clarify that this standard applies to processing before cryopreservation.Item 11 is new to the proposed edition. This is a requir

48、ement that is arguably inherent in general quality system requirements though the CT SPU elected to explicitly state the requirement in this standard.5.18Storage and PreservationThe facility shall establish and maintain policies, processes, and procedures for storage of materials and cellular therap

49、y products in order to prevent mix-ups, limit deterioration, contamination, cross-contamination, and improper distribution of cellular therapy products limit deterioration and prevent damage. This shall include the use of designated, secure storage areas with controlled access.The CT SPU elected to

50、add the elements in bold to expand the scope of the standard.!CStorage at Processing FacilityFor each type of cellular therapy product, tThe facility shallestablish product storage specifications and acceptablestorage conditions, including temperature range and/orliquid nitrogen level to mai

51、ntain viability and function.Standard applies..1Storage devices shall have the capacity anddesign to ensure that proper temperatureand/or liquid nitrogen level is maintained.!C.2Storage devices containing cellular therapyproducts and critical materials shall have asystem to

52、continuously monitor and recordat defined time intervals, the temperatureand/or liquid nitrogen levels.Minor changes made for clarity.PROPOSED Standards for Cellular Therapy Product Services, 4th edition7Draft for comment purposes onlyComment period: May 29 July 29, 2009!CStability of Cryopr

53、eserved ProductsFor each type of cellular therapy product, a set of product specifications shall be established. The stability of each type of cellular therapy Cryopreserved products during storage shall be monitored through a stability program. Sampling and evaluation shall be performed, at a minim

54、um, on an annual basis.The CT SPU edited the standard and limited the application of a stability program to cryopreserved products..1NEW STANDARD At a minimum, the stability program shall include product container integrity, and viable cell recovery.Standard .1 is new to the proposed

55、 4th edition.There shall be aliquots of stored cellular therapy products preserved and retained under storage conditions equivalent to those of the cellular therapy product. Integral segments shall be used when appropriate. The use and disposition of these aliquots shall be defined in the fa

56、cilitys policies, processes and procedures.The CT SPU elected to remove the sentence concerning integral segments. The standard concerning the requirement to use integrally attached segments for cord blood products remains in ..1.1Special Requirements for Cord Blood Cord blood products shall have at least two integrally attached segments cryopreserved with the product. Standard and Reference Standard 5.17B, Processing Tests f