Guidance for Industry 
Current Good Tissue Practice (CGTP) 
and Additional Requirements for 
Manufacturers of Human Cells, 
Tissues, and Cellular and Tissue-Based 
Products (HCT/Ps) 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852- 
1448, or by calling 1-800-835-4709 or 301-827-1800, or e-mail ocod@fda.hhs.gov, or from the 
Internet at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida 
nces/default.htm. 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or e-mail 
address listed above. 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
December 2011   
Contains Nonbinding Recommendations 
Table of Contents 
I.  INTRODUCTION ............................................................................................................. 1 
II.  BACKGROUND................................................................................................................ 1 
A.  What is the Scope of this Guidance? ................................................................... 1 
B.  Who Should Read this Guidance? ....................................................................... 2 
III.  CGTP REQUIREMENTS ( 1271.150) .......................................................................... 3 
A.  What Are Core CGTP Requirements? ............................................................... 3 
B.  What Requirements Must I Follow if I Perform Only Some Manufacturing 
Operations? ............................................................................................................ 4 
C.  How Do I Ensure that Another Establishment with Which I Have a Contract, 
Agreement or Other Arrangement Complies with CGTP Requirements? ..... 4 
D.  What Steps Should I Take if I Become Aware and Then Determine that the 
Establishment Performing Any Step in Manufacture for Me is No Longer in 
Compliance with Part 1271? ................................................................................ 6 
E.  Do I Have to Follow CGTP Requirements if My HCT/Ps Are Also Regulated 
as a Biological Product, Drug, or Device?........................................................... 6 
F.  Am I Responsible for Following All of the CGTP Requirements? ................... 9 
IV.  EXEMPTIONS AND ALTERNATIVES ( 1271.155) ................................................ 10 
A.  How Do I Request an Exemption or Alternative from Part 1271, Subpart C 
or D? ..................................................................................................................... 10 
B.  Where Do I Send a Request for an Exemption or Alternative? ...................... 10 
C.  Can an Exemption or Alternative Apply to More Than One Establishment? 
. .............................................................................................................................. 10 
V.  ESTABLISHMENT AND MAINTENANCE OF A QUALITY PROGRAM ........... 11 
( 1271.160) .................................................................................................................................. 11 
A.  What is a Quality Program? .............................................................................. 11 
B.  Which Establishments Must Establish and Maintain a Quality Program? ... 11 
C.  What is the Role of the Quality Program Regarding Procedures? ................ 11 
D.  What Must I Do When Information is Received From Sources Outside the 
Establishment, and What Must I Do with this Information? ......................... 12 
E.  With Whom Must an Establishment Share Information Pertaining to the 
Possible Contamination of or Potential for Transmission of Communicable 
Disease by an HCT/P? ......................................................................................... 12 
F.  How Can a Quality Program Ensure that Appropriate Corrective Actions 
Related to Core CGTP Requirements Are Taken, When Necessary? ........... 13 
G.  What Must the Quality Program Ensure Regarding Personnel? ................... 14 
H.  How Does the Quality Program Ensure that Appropriate Monitoring 
Systems Are in Place? ......................................................................................... 14 
I.  When HCT/P Deviations Occur, What is the Role of the Quality Program? 15 
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Contains Nonbinding Recommendations 
J.  What Are the Requirements for Performing Quality Audits of Your 
Establishment?..................................................................................................... 15 
K.  Will FDA Review the Quality Audit During Inspection of the Establishment? 
. .............................................................................................................................. 15 
L.  If the Establishment Relies on Computer Software to Comply with Core 
CGTP Requirements, What Activities Must be Performed Before 
Implementing the Software? .............................................................................. 16 
VI.  PERSONNEL ( 1271.170) ............................................................................................. 17 
A.  What Are the Specific Requirements for Personnel at HCT/P 
Establishments? ................................................................................................... 17 
B.  How Would I Ensure that Personnel Have the Necessary Education, 
Experience and Training to Perform Their Job? ............................................. 17 
VII.  PROCEDURES ( 1271.180) .......................................................................................... 17 
A.  What Do I Need to do Before Implementing New Procedures Related to Core 
CGTP Requirements? ........................................................................................ 18 
B.  Do Procedures Have to be Physically Maintained in the Area Where the 
Operation is Performed? .................................................................................... 18 
C.  May I Use Procedures From Established Industry Standards? ..................... 18 
VIII.  FACILITIES ( 1271.190) .............................................................................................. 18 
A.  What Are General Requirements for HCT/P Facilities?................................. 18 
B.  What Facility Cleaning and Sanitation Issues Must I Consider? ................... 19 
C.  Is it Necessary to Perform Different Operations in Separate Areas Within a 
Facility? ................................................................................................................ 19 
D.  What Facility-Related Procedures Must I Establish and Maintain? ............. 20 
E.  What Facility-Related Documentation Must I Maintain? ............................... 20 
F.  How Do Facility-Related Requirements Apply to Recovery of HCT/Ps? ...... 20 
IX.  ENVIRONMENTAL CONTROL AND MONITORING ( 1271.195) ...................... 21 
A.  What Environmental Controls Must I Have in Place at My Facility? ........... 21 
B.  How Often Must I Inspect My Environmental Control Systems? .................. 21 
C.  Is Environmental Monitoring Required? ......................................................... 22 
D.  What Temperature and Humidity Factors Should be Considered for 
Environmental Control and Monitoring? ......................................................... 22 
E.  How Often Should I Perform Environmental Monitoring? ............................ 22 
F.  Are records related to environmental control and monitoring required? ..... 23 
G.  What Procedures Related to Environmental Control and Monitoring Must I 
Establish and Maintain?..................................................................................... 23 
H.  What Environmental Control and Monitoring Issues Should be Considered 
for Recovery of HCT/Ps? .................................................................................... 23 
X.  EQUIPMENT ( 1271.200) ............................................................................................. 24 
A.  What Are the General Equipment Requirements? .......................................... 24 
B.  Do I Have to Qualify or Certify Equipment (Installation Qualification, 
Operational Qualification, Performance Qualification)? ............................... 24 
  ii   
Contains Nonbinding Recommendations 
C.  Does Recovery Equipment (e.g., Instruments) Have to be Segregated by 
Donor Prior to Cleaning in an Automated Washer? ....................................... 25 
D.  Is There Any Prohibition on the Re-Use of Cleaning/Disinfection Solutions, 
or Containers Used to Clean and Disinfect Instruments? ............................... 25 
E.  Are There Special Considerations for Cleaning and Sanitizing Equipment at 
Risk for Transmissible Spongiform Encephalopathy Contamination? ......... 25 
F.  What Procedures and Schedules Are Required for Equipment? ................... 26 
G.  What Equipment Calibration Must I Perform? .............................................. 26 
H.  What Equipment Inspections Must I Perform? ............................................... 26 
I.  What Records Related to Equipment Must I Keep? ....................................... 27 
J.  What Are the Responsibilties of Recovery Establishments that Contract the 
Cleaning and Sterilization of Recovery Instruments (Equipment)? .............. 27 
XI.  SUPPLIES AND REAGENTS ( 1271.210) .................................................................. 28 
A.  What Are Supplies and Reagents? .................................................................... 28 
B.  What Verification is Required for Supplies and Reagents? ............................ 28 
C.  What Are Some Methods to Verify Reagents or Supplies? ............................. 29 
D.  Are Reagents Required to be Sterile? ............................................................... 29 
E.  What is Required of Reagents I Produce In-House? ....................................... 29 
F.  What Records Must I Keep Related to Supplies and Reagents? .................... 29 
G.  What Procedures Related to Supplies and Reagents Must I Establish and 
Maintain? ............................................................................................................. 30 
XII.  RECOVERY ( 1271.215) .............................................................................................. 30 
A.  What Procedures and Records Related to Recovery Are Required? ............. 30 
B.  What Are Some Ways that a Recovery Establishment Could Ensure that 
HCT/Ps Are Recovered 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? ....... 31 
C.  What Are Ways in Which a Recovery Establishment Could Identify the 
Donor Prior to HCT/P Recovery? ..................................................................... 32 
D.  What Are Ways in Which a Processor Receiving HCT/Ps From a Recovery 
Establishment Under Contract with the Processor Could Verify the Identity 
of the Donor and Could Ensure That the Donor Records Are From the Same 
Donor as the HCT/Ps? ........................................................................................ 32 
XIII.  PROCESSING AND PROCESS CONTROLS ( 1271.220) ....................................... 33 
A.  What is Processing? ............................................................................................ 33 
B.  May I Pool HCT/Ps? ........................................................................................... 34 
C.  What in-Process Control and Testing Must I Perform? ................................. 34 
D.  Why Are Pre-Processing (Microbiological) Cultures Important? .................. 35 
E.  Are HCT/Ps Required to be Sterile? ................................................................. 36 
F.  What Special Processing and Process-Control Considerations Must I Have 
for Dura Mater? .................................................................................................. 36 
XIV.  PROCESS CHANGES ( 1271.225) .............................................................................. 37 
XV.  PROCESS VALIDATION ( 1271.230) ........................................................................ 37 
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Contains Nonbinding Recommendations 
A.  What are General Requirements for Process Validation? .............................. 37 
B.  What is the Difference Between Validation and Verification?........................ 38 
C.  How Do I Perform a Validation Study? ............................................................ 38 
D.  What Information Should I Collect for Processes that Must be Validated?. 39 
E.  What is Required if I Make a Written Representation That My Processing 
Methods Reduce the Risk of Transmission of Communicable Disease by an 
HCT/P? ................................................................................................................ 39 
F.  What Must I Do When I Make Changes to a Validated Process? .................. 39 
XVI.  LABELING CONTROLS ( 1271.250) ......................................................................... 40 
A.  What Procedures Must I Establish and Maintain to Control the Labeling of 
My HCT/Ps? ........................................................................................................ 40 
B.  What Control Procedures Must I Use to Verify Label Accuracy, Legibility, 
and Integrity? ...................................................................................................... 40 
C.  What Labeling Requirements Apply to My HCT/P? ...................................... 41 
D.  Do the CGTP Regulations Specify When Labels Are to be Placed on HCT/P 
Containers? .......................................................................................................... 41 
XVII. STORAGE ( 1271.260) .................................................................................................. 41 
A.  What Storage Area Activities Must I Control? ................................................ 41 
B.  How Do I Determine Appropriate Storage Temperatures for My HCT/Ps? 42 
C.  How Do I Determine Whether an Expiration Date Must be Assigned to My 
HCT/Ps? ............................................................................................................... 42 
D.  What Should I Do When Proper Storage Conditions Are Not Met? ............. 43 
E.  What Temperature Limits Must I Establish During Manufacturing? ........... 43 
F.  What Procedures Related to Storage Must I Establish and Maintain? ......... 43 
XVIII. RECEIPT, PREDISTRIBUTION SHIPMENT, AND DISTRIBUTION OF AN 
HCT/P ( 1271.265) ......................................................................................................... 43 
A.  What Should I Do Before Accepting an HCT/P From Another 
Establishment?..................................................................................................... 43 
B.  What Are Ways That I Can Evaluate an Incoming HCT/P for 
Microorganisms and Inspect for Damage and Contamination? ..................... 44 
C.  What is Predistribution Shipment? ................................................................... 44 
D.  When is an HCT/P Available for Distribution? ............................................... 45 
E.  What Must I Do Before Making an HCT/P Available for Distribution? ....... 45 
F.  Who Must Determine That an HCT/P is Available for Distribution? ........... 46 
G.  May I Release an HCT/P if it Has Been Manufactured Under a Departure 
From a Procedure?.............................................................................................. 46 
H.  Does a Distributor Need to Make an Assessment that the HCT/P is Available 
for Distribution? .................................................................................................. 46 
I.  Am I Required to Validate or Verify Packaging and Shipment of HCT/Ps? 47 
J.  Am I Required to Determine the Appropriate Shipping Conditions? ........... 47 
K.  What Procedures and Documentation Must I Have for Receipt, 
Predistribution Shipment, and Distribution of an HCT/P? ............................ 47 
L.  Is an Establishment Such as a Hospital That Only Receives and Stores 
HCTP/s Required to Register Under  1271.1(b)? .......................................... 47 
  iv   
Contains Nonbinding Recommendations 
M.  Am I Permitted to Place Returned HCT/Ps Back Into Inventory? ................ 48 
XIX.  RECORDS ( 1271.270) .................................................................................................. 48 
A.  What are the General Requirements for Records? .......................................... 48 
B.  What Kind of Records Management System Must I Have? ........................... 48 
C.  What Are Acceptable Methods of Record Retention? ..................................... 49 
D.  For How Long Must I Retain my HCT/P Manufacturing Records? .............. 49 
E.  What Records of Contracts and Agreements Must I Maintain? .................... 50 
XX.  TRACKING ( 1271.290) ............................................................................................... 50 
A.  How Extensive a Tracking System Must I Establish and Maintain? ............. 50 
B.  Must Each HCT/P Have a Distinct Identification Code? ................................ 51 
C.  How Do I Ensure Tracking of HCT/Ps Distributed From My Establishment 
to Consignees or for Final Disposition? ............................................................. 51 
D.  Are There Specific Requirements for Dura Mater Donors? ........................... 52 
XXI.  COMPLAINT FILE ( 1271.320) .................................................................................. 52 
A.  What Information About Each Complaint Must I Have in My Complaint 
File? ...................................................................................................................... 52 
B.  How Should I Review and Evaluate Complaints? ............................................ 53 
XXII. REPORTING ( 1271.350) ............................................................................................. 53 
A.  What Are the General Requirements for Adverse Reaction Reports? .......... 53 
B.  What is Considered a Medical or Surgical Intervention That I Must Report 
to FDA? ................................................................................................................ 55 
C.  How Do I Report Adverse Reactions to FDA? .................................................. 55 
D.  What Kind of Information Should I Review When Investigating Adverse 
Reactions? ............................................................................................................ 55 
E.  When Do I Submit a Followup Report to FDA? ............................................... 56 
F.  What Procedures Did FDA Develop to Handle Adverse Reaction Reports for 
HCT/Ps? ............................................................................................................... 56 
G.  How Do I Report an HCT/P Deviation to FDA? .............................................. 56 
H.  What Are the General Requirements for HCT/P Deviation Reporting? ....... 57 
XXIII. LABELING ( 1271.370) ................................................................................................ 57 
A.  What Information Must Appear on the HCT/P Label? .................................. 57 
B.  Is the Manufacturer Expected to Place the Distinct Identification Code on 
Information That Accompanies Each Distributed HCT/P? ........................... 58 
C.  What Additional Information Must Appear on the HCT/P Label or 
Accompany the HCT/P? ..................................................................................... 58 
D.  How Can I Maintain Privacy with Regard to the Warning Statements? ...... 58 
E.  Must the Name and Address of the Processing Establishment, if Different 
From the Establishment That Determines That the HCT/P Meets Release 
Criteria and Makes it Available for Distribution, be Included on the Label or 
Other Accompanying Information Provided to the Consignee? .................... 59 
XXIV. REFERENCES ................................................................................................................ 60 
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Contains Nonbinding Recommendations 
Guidance for Industry 
Current Good Tissue Practice (CGTP) and Additional 
Requirements for Manufacturers of Human Cells, Tissues, and 
Cellular and Tissue-Based Products (HCT/Ps) 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on 
  this topic.  It does not create or confer any rights for or on any person and does not operate 
  to bind FDA or the public. You can use an alternative approach if the approach satisfies the 
  requirements of the applicable statutes and regulations. If you want to discuss an alternative 
  approach, contact the appropriate FDA staff. If you cannot identify the appropriate FDA 
  staff, call the appropriate number listed on the title page of this guidance. 
 
 
I.  INTRODUCTION 
 
We, FDA, are issuing this guidance to provide you, establishments that manufacture human 
cells, tissues, and cellular and tissue-based products (HCT/Ps), with recommendations for 
complying with Current Good Tissue Practice (CGTP) requirements under Title 21 Code of 
Federal Regulations, Part 1271 (21 CFR Part 1271), Subpart D (Subpart D)1, and requirements 
under Part 1271, Subpart E. This guidance also addresses whether the establishment registration 
and HCT/P listing requirements under Part 1271, Subparts A and B (Subparts A and B) apply in 
certain instances.  This guidance finalizes the draft guidance of the same title dated January 
2009. 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the FDAs current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited. 
The use of the word should in FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
A.  What is the Scope of this Guidance? 
 
This guidance provides recommendations for complying with the requirements under Part 
1271, Subparts D and E, during manufacture of HCT/Ps.  However, at this time Subpart 
D (with the exception of 21 CFR 1271.150(c) and 1271.155) and Subpart E do not apply 
to reproductive HCT/P establishments regulated solely under section 361 of the Public 
 
1 The requirements of Part 1271, Subpart C (Donor Eligibility) are a component of CGTP requirements 
( 1271.45(a)); however, this guidance does not directly address Part 1271, Subpart C requirements. 
  1   
Contains Nonbinding Recommendations 
Health Service (PHS Act).2 While this guidance applies to establishments that 
manufacture HCT/Ps that meet the criteria listed in  1271.10 and are regulated solely 
under section 361 of the PHS Act and the regulations in 21 CFR Part 1271,3 we note that 
the CGTP requirements also apply to HCT/Ps regulated as drugs, devices, and/or 
biological products under section 351 of the PHS Act and/or the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) (see  1271.1(b)(2)). This guidance also addresses 
whether the establishment registration and HCT/P listing requirements under Part 1271, 
Subparts A and B, apply in certain instances. 
 
For additional information on Subparts C and E refer to the following FDA guidances 
entitled, Guidance for Industry: Eligibility Determination for Donors of Human Cells, 
Tissues, and Cellular and Tissue-Based Products (HCT/Ps) dated August 2007 (Ref. 1); 
and Guidance for Industry, MedWatch Form FDA 3500A: Mandatory Reporting of 
Adverse Reactions Related to Human Cells, Tissues, and Cellular and Tissue-Based 
Products (HCT/Ps) dated November 2005 (Ref. 2). 
 
B.  Who Should Read this Guidance? 
 
This guidance is intended for any HCT/P establishment that performs a manufacturing 
step and is responsible for complying with CGTP requirements. The term 
establishment, as defined under  1271.3(b), means a place of business under one 
management, at one general physical location, that engages in the manufacture of 
HCT/Ps. The term includes any individual, partnership, corporation, association, or other 
legal entity engaged in the manufacture of HCT/Ps, and facilities that engage in contract 
manufacturing services for a manufacturer of HCT/Ps. 
 
Establishments may engage another establishment under a contract, agreement, or other 
arrangement to perform any manufacturing step. Such allocations of responsibility must 
comply with  1271.150(c), and the other establishments must also comply with the 
requirements applicable to the manufacturing steps they perform. 
 
In this guidance, you means: 
 
  the establishment that performs a manufacturing step; or 
  the establishment that performs a manufacturing step under contract, 
agreement or other arrangement for another HCT/P establishment. 
 
 
 
 
 
2 With two exceptions as specified, the regulations in subparts D and E have not being finalized with respect to 
reproductive HCT/Ps described in  1271.10 and regulated solely under section 361 of the PHS Act and the 
regulations in part 1271. The docket remains open, and we ask that interested parties submit comments on 
communicable disease risks associated with reproductive HCT/Ps and appropriate regulation to minimize those risks 
(other than that stipulated in part 1271 subparts A, B, C, and F, and  1271.150(c) and 1271.155 in subpart D) 69 
FR 68612, November 2004. 
3 An HCT/P that falls into this category is referred to as a 361 HCT/P. 
  2   
Contains Nonbinding Recommendations 
III.  CGTP REQUIREMENTS ( 1271.150) 
 
CGTP requirements govern the methods used in, and the facilities and controls used for, the 
manufacture of HCT/Ps in a way that prevents the introduction, transmission, or spread of 
communicable diseases by HCT/Ps ( 1271.150(a)).4 Manufacture, as defined in 
 1271.3(e), 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. Under  1271.145, 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. Under  1271.150(a), 
communicable diseases include, but are not limited to, those transmitted by viruses, bacteria, 
fungi, parasites, and transmissible spongiform encephalopathy agents. 
 
A.  What Are Core CGTP Requirements? 
 
Core CGTP requirements ( 1271.150(b)) are those requirements that directly relate to 
preventing the introduction, transmission, or spread of communicable disease by HCT/Ps. 
The core CGTP requirements include requirements for: 
 
  facilities ( 1271.190(a) and (b)); 
  environmental control ( 1271.195(a)); 
  equipment ( 1271.200(a)); 
  supplies and reagents ( 1271.210(a) and (b)); 
  recovery ( 1271.215); 
  processing and process controls ( 1271.220); 
  labeling controls ( 1271.250(a) and (b)); 
  storage (1271.260(a) through (d)); 
  receipt, predistribution shipment, and distribution of an HCT/P ( 1271.265(a) 
through (d)); and 
  donor eligibility determinations, donor screening, and donor testing 
( 1271.50, 1271.75, 1271.80, and 1271.85). 
 
Other CGTP requirements discussed in this guidance support the core CGTP 
requirements (e.g., the required records management system in  1271.270(b)). Although 
we have identified core CGTP requirements, you must follow all CGTP requirements 
( 1271.150(a)).  If you perform only some manufacturing operations, see 
 1271.150(c)(1)(i) and section III.B. of this guidance. 
 
 
 
 
 
 
 
 
 
4 The CGTP provisions specifically governing determinations of donor eligibility, including donor screening and 
testing, are set out separately in Part 1271, Subpart C. 
  3   
Contains Nonbinding Recommendations 
B.  What Requirements Must I Follow if I Perform Only Some Manufacturing 
Operations? 
 
Under  1271.150(c)(1)(i), you must comply with those requirements applicable to the 
operations that you perform. Under  1271.150(c)(1)(ii), if you engage another 
establishment (e.g., a laboratory performing communicable disease testing, or an 
irradiation facility performing terminal sterilization of an HCT/P) under a contract, 
agreement, or other arrangement to perform any step in manufacture for you, that 
establishment must comply with the requirements applicable to that manufacturing step. 
 
C.  How Do I Ensure that Another Establishment with Which I Have a Contract, 
Agreement or Other Arrangement Complies with CGTP Requirements? 
 
Under  1271.150(c)(1)(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. 
 
Some ways that you could ensure the other establishments compliance with applicable 
CGTP requirements, include the following: 
 
  ensure that responsibilities are listed and understood as they relate to CGTP 
requirements; 
  review test kit package inserts that are used by a contract test laboratory; 
  review standard operating procedures (SOPs) applicable to CGTP 
requirements; 
  review certifications (e.g., Clinical Laboratory Improvement Act (CLIA), 
certificate of analysis), where appropriate; 
  review previous compliance actions such as Form FDA 483 and 
Establishment Inspection Reports (EIRs); 
  perform for-cause and random comparisons of documentation provided by 
your contractor with source documents from the originator of the material; 
  ensure that the establishment has a quality program that addresses the 
operations that it performs for you; and/or 
  perform periodic audits of the establishment. We recommend that such an 
audit include a review of compliance with all Part 1271 requirements 
applicable to the operations that the establishment performs for you. 
 
Example 1: You are a processor that receives HCT/Ps from a recovery establishment 
under contract with you. You have decided to audit the recovery establishment annually 
to ensure compliance with CGTP requirements for recovery, donor medical history 
interview, obtaining specimens for communicable disease testing, and shipping HCT/Ps 
to you at appropriate temperatures. During the audit, you should consider reviewing a 
representative sample of the records that were previously provided by the recovery 
establishment to confirm their accuracy by checking with the source of the information 
(e.g., directly contacting the attending physician, the communicable disease testing 
  4   
Contains Nonbinding Recommendations 
laboratory, the coroner, or the hospital). You also may want to accompany the recovery 
team on a recovery to review adherence to procedures and to review the quality program 
activities. 
 
Example 2: You should ensure that your contract laboratories that perform HCT/P donor 
testing have the appropriate CLIA certification and ensure that they are using the 
appropriate FDA-licensed, approved, or cleared donor screening tests according to the 
manufacturers instructions (e.g., by reviewing a listing of the tests and copies of the test 
kit package insert). Such laboratories are considered establishments ( 1271.3(b)) that 
manufacture ( 1271.3(e)) HCT/Ps and are required to register with FDA ( 1271.21). 
You should review their most recent validated Form FDA 3356 for registration and 
listing to ensure that they are in compliance with  1271.10(b). They must also have a 
quality program appropriate for the operations they perform ( 1271.160(a)). You should 
consider including in your contract, agreement, or other arrangement with an 
establishment a requirement that the establishment provide you with all Form FDA 483s 
and EIRs that it receives, and copies of its SOPs, and a requirement to be notified of 
proposed changes to any test kit or testing methodology being used. After your initial 
assessment to ensure that the establishment performing the manufacturing step for you is 
in compliance, you should check periodically to ensure its continued operational 
compliance. 
 
Example 3: You contract out some of your processing steps such as terminal sterilization 
and microbial testing. You should have assurance that your contractors processing steps 
have been verified or validated to be in compliance with all of the applicable 
requirements in  1271 including, but not limited to,  1271.220, 1271.225, and 
1271.230, and that your contractor has a quality program that addresses the SOPs and 
records applicable to core CGTPs, including 21 CFR 1271.220 ( 1271.160(a)). 
 
Example 4: You are the establishment that determines that an HCT/P meets all release 
criteria and you make 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 Part 
1271, Subparts C and D, and any other applicable requirements ( 1271.150(c)(2)). 
 
Example 5: You contract out the actual distribution of your product. You should ensure 
that distribution records are kept so that HCT/Ps can be tracked back to you if you are the 
establishment that makes the HCT/P available for distribution (see  1271.150(c)(2)). 
You should also review copies of applicable storage SOPs to ensure that your distributed 
HCT/Ps are stored according to your specifications. 
  5   
Contains Nonbinding Recommendations 
D.  What Steps Should I Take if I Become Aware and Then Determine that the 
Establishment Performing Any Step in Manufacture for Me is No Longer in 
Compliance with Part 1271? 
 
Under  1271.150(c)(1)(iii), if you become aware that the establishment may no longer 
be in compliance with applicable CGTP requirements, you must take reasonable steps to 
ensure the establishment complies with those requirements. These steps may include 
reviewing the establishments corrective action plan and verifying that corrective actions 
have been taken under the establishments quality program. 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 ( 1271.150(c)(1)(iii)). 
 
E.  Do I Have to Follow CGTP Requirements if My HCT/Ps Are Also Regulated 
as a Biological Product, Drug, or Device? 
 
Yes, CGTP requirements as well as drug current good manufacturing practice (CGMP) 
requirements or device quality system (QS) regulation requirements apply. The current 
CGMP regulations in 21 CFR Parts 210 and 211 (Parts 210 and 211) or the QS regulation 
in 21 CFR Part 820 (Part 820) apply to an HCT/P depending upon whether the product is 
regulated as a drug, device or biological product ( 1271.150(d)) (see especially, 
 210.1(c), 210.2, 211.1, and 820.1). These CGMP and QS regulations supplement the 
CGTP requirements, and in the event that a regulation in Part 1271 is in conflict with a 
requirement in Parts 210, 211, or 820, the regulations more specifically applicable to the 
product in question will supersede the more general. 
 
1.  For HCT/Ps regulated as biological products  Current Good Tissue Practice 
and Current Good Manufacturing Practice requirements 
 
HCT/Ps regulated as biological products are regulated under sections 351 and 361 
of the PHS Act and the FD&C Act. These HCT/Ps include some hematopoietic 
progenitor cells (HPCs) and other cellular products (e.g., allogeneic pancreatic 
islet cells, cell-based cancer vaccines and immunotherapies, chondrocytes). 
CGTP requirements govern the methods used in, and the facilities and controls 
used for, the manufacture of HCT/Ps to prevent the introduction, transmission, or 
spread of communicable diseases by HCT/Ps. 
 
The CGMP requirements in Parts 210 and 211 govern the methods to be used in, 
and the facilities or controls to be used for, the manufacture, processing, packing, 
or holding of a drug to ensure that such drug meets the requirements of the FD&C 
Act as to safety, and has the identity and strength and meets the quality and purity 
characteristics that it purports or is represented to possess. These CGMP 
requirements apply to biological products, regulated under section 351 of the PHS 
Act, that meet the definition of drug in the FD&C Act. Due to the broader scope 
of these regulations, most of the CGMP regulations under Parts 210 and 211 
would apply to HCT/Ps regulated as biological products. In many instances, the 
  6   
Contains Nonbinding Recommendations 
CGMP regulations and CGTP regulations require the same manufacturing 
practice, and compliance with the CGMP regulations results in compliance with 
the applicable CGTP requirements. 
 
However, for the following CGTP requirements, the CGTP requirement would 
require additional manufacturing practices, because the CGTP requirements 
would not be partly or completely covered by a corresponding CGMP regulation 
requiring the same practice:5 6 
 
  all donor eligibility requirements (Part 1271, Subpart C); 
  prevention of the introduction, transmission, or spread of communicable 
diseases ( 1271.145); 
  certain parts of manufacturing arrangements under a contract, agreement, or 
other arrangements ( 1271.150(c)(1)(ii) and (iii)); 
  procedures for sharing with other establishments information pertaining to 
possible contamination or potential for transmission of communicable disease 
( 1271.160(b)(2)); 
  audits ( 1271.160(c)); 
  prohibition on pooling ( 1271.220(b)); 
  predistribution shipment ( 1271.265(b)); 
  HCT/P availability for distribution only after donor eligibility established 
( 1271.265(c)(2)); 
  packaging and shipping requirements ( 1271.265(d)); 
  recordkeeping for 10 years ( 1271.270(d)) (but facility cleaning and 
sanitation records for 3 years ( 1271.190(d)(2)); and 
  tracking ( 1271.290(a) through (g)). 
 
An example in which a corresponding CGMP requirement partially covers a 
CGTP requirement is the quality program requirement ( 1271.160). Some 
quality program requirements are covered by specific subparts and sections of 
Part 211 such as  211.22 (quality control unit), Part 211, Subpart F (production 
and process controls),  211.160(a) (specifications and standards, sampling plans, 
and test procedures, reviewed and approved by the quality control unit), 
 211.192 (production record review), and  211.198 (complaint files). If you 
manufacture HCT/Ps that are regulated as biological products, you must follow 
these Part 211 requirements, as well as certain requirements found under 
 1271.160. 
 
 
 
 
5 As discussed in section IV of this guidance, you may request an exemption from or alternative to any requirement 
in Part 1271, Subpart C or D ( 1271.155). 
6 Under  210.1(c), the manufacturer of an HCT/P regulated as a drug, including a biological product that is a drug 
under the FD&C Act, must comply with the donor eligibility procedures in Part 1271, Subpart C. Failure to follow 
the CGMP requirements, including the testing and screening procedures in Part 1271, would make the product 
adulterated under the FD&C Act. Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and 
Tissue-Based Products [69 FR 29788, May 25, 2004] 
  7   
Contains Nonbinding Recommendations 
An example in which a CGTP requirement is not covered by a CGMP 
requirement is the CGTP requirement for predistribution shipment in 
 1271.265(b). Under  1271.265(b), if you ship an HCT/P within your 
establishment or between establishments (e.g., shipment from a procurer to a 
processor), and the HCT/P is not available for distribution as described in 
 1271.265(c), then 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. 
 
2.  For HCT/Ps regulated as medical devices 
 
HCT/Ps regulated as medical devices are also regulated under section 361 of the 
PHS Act and the FD&C Act. CGTP requirements and the Quality System (QS) 
regulations in Part 820 are applicable. 
 
An example of an HCT/P regulated as a medical device is demineralized bone 
combined with a handling agent. The QS regulation would apply to HCT/Ps that 
are not regulated solely under section 361 of the PHS Act and meet the definition 
of devices in the FD&C Act. In many instances, the QS regulation and the CGTP 
regulation would require the same manufacturing practice, and compliance with 
the QS regulations would result in compliance with applicable CGTP 
requirements. An example in which the corresponding sections of the QS 
regulation completely cover the CGTP requirements are the requirements for 
acceptance activities and nonconforming products. Therefore, if you manufacture 
HCT/Ps regulated as medical devices and comply with  820.50, 820.80, 820.86, 
and 820.90, you would also be in compliance with the analogous CGTP 
requirements in  1271.60, 1271.210, and 1271.265. 
 
However, for the following CGTP requirements, the CGTP requirement would 
require additional manufacturing practices, because the CGTP requirements 
would not be partly or completely covered by a corresponding QS regulation 
requiring the same practice: 7 
 
  all donor eligibility requirements (Part 1271, Subpart C); 
  prevention of the introduction, transmission, or spread of communicable 
diseases ( 1271.145); 
  certain parts of manufacturing arrangements, under a contract, or other 
arrangements ( 1271.150(c)(1)(ii) and (iii)); 
  procedures for sharing with other establishments information pertaining to 
possible contamination or potential for transmission of communicable disease 
( 1271.160(b)(2)); 
  prohibition on pooling ( 1271.220(b)); 
  predistribution shipment ( 1271.265(b)); 
 
 
7 As discussed in section IV of this guidance, you may request an exemption from or alternative to any requirement 
in Part 1271, Subpart C or D ( 1271.155). 
  8   
Contains Nonbinding Recommendations 
  HCT/P availability for distribution only after donor eligibility established 
( 1271.265(c)(2)); 
  packaging and shipping requirements ( 1271.265(d)); 
  recordkeeping for 10 years ( 1271.270(d)) (but facility cleaning and 
sanitation records for 3 years ( 1271.190(d)(2)); and 
  tracking ( 1271.290(a) through (g)). 
 
An example in which the corresponding section of a QS regulation partially 
covers a CGTP requirement are the requirements for a quality program. Quality 
program requirements in Part 1271 that are partially covered by specific sections 
in Part 820 include  820.5 (Quality System),  820.20(a) through (e) 
(Management Responsibility),  820.22 (Quality Audit),  820.70 (Production 
and Process Controls), and  820.100 (Corrective and Preventive Action). 
Specific sections of Part 1271 not covered by the requirements in Part 820 include 
 1271.160(b)(1) and (b)(2). If you manufacture HCT/Ps regulated as medical 
devices, you must follow the aforementioned in Parts 820 and 1271.160(b)(1) and 
(b)(2). 
 
An example of a CGTP requirement in which there is no corresponding section of 
the QS regulation is the CGTP requirement prohibiting pooling in  1271.220(b). 
HCT/Ps regulated as medical devices that are from two or more donors must not 
be pooled (placed in physical contact or mixed in a single receptacle) during 
manufacturing under this regulation ( 1271.220(b)). 
 
 
F.  Am I Responsible for Following All of the CGTP Requirements? 
 
You will find that many of the requirements are qualified by where appropriate. Under 
 1271.150(e), a requirement is deemed to be appropriate, unless you can document 
justification otherwise. What this means is that each establishment has the flexibility to 
determine if the requirement is appropriate for your establishment. Specifically, 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 ( 1271.150(e)). Thus, in general, 
a requirement is appropriate if it helps you to ensure that the HCT/P is not contaminated 
or cross-contaminated or if it helps you to carry out any needed corrective actions. 
 
For example, an establishment that processes HCT/Ps has determined that the 
 1271.195(a)(1) environmental monitoring requirement for temperature and humidity 
control is not applicable because the establishment determined that the temperature and 
humidity would not affect the introduction, transmission or spread of communicable 
disease. If you determine that a requirement is not appropriate for your establishment, 
you must document justification of that determination ( 1271.150(e)). 
  9   
Contains Nonbinding Recommendations 
 
 
IV.  EXEMPTIONS AND ALTERNATIVES ( 1271.155) 
 
A.  How Do I Request an Exemption or Alternative from Part 1271, Subpart C 
or D? 
 
Under  1271.155(d), you must ordinarily request an exemption or alternative in writing 
(hardcopy or electronically). The request must be accompanied by all relevant valid 
scientific data ( 1271.155(b)) and either information justifying the requested exemption 
from the requirement ( 1271.155(b)(1)) or a description of a proposed alternative 
method of meeting the requirement ( 1271.155(b)(2)). 
 
You may request an exemption orally if circumstances make it difficult (e.g., there is 
inadequate time) to submit your request in writing ( 1271.155(d)). You must follow an 
oral request with an immediate written request ( 1271.155(d)), which must be 
accompanied by supporting documentation, including all relevant valid scientific data 
( 1271.155(b)). 
 
Only after we grant the request may you begin operating under the exemption or 
alternative ( 1271.155(e)). You must maintain documentation of FDAs grant of the 
exemption or alternative and the date on which you began operating under the terms of 
the exemption or alternative at the establishment ( 1271.155(f)). We describe the 
procedures used to address requests for exemptions and alternative procedures in 
standard operating policies and procedures (SOPP) 9151 (Ref. 3). 
 
B.  Where Do I Send a Request for an Exemption or Alternative? 
 
Submit your request to the Director of the appropriate FDA center. If the HCT/P is 
regulated solely under  1271.10 as a 361 HCT/P, or as a biological product or a medical 
device regulated by the Center for Biologics Evaluation and Research (CBER), send your 
request to the Director, CBER. If the HCT/P is regulated as a medical device by the 
Center for Devices and Radiological Health (CDRH), send your request to the Director, 
CDRH. We provide more specific information on the process, including addresses and 
contacts, at https://www.fda.gov/vaccines-blood-biologics/tissue-tissue-
products/exemptions-and-alternatives. 
 
C.  Can an Exemption or Alternative Apply to More Than One Establishment? 
 
A granted exemption or alternative is only applicable to the establishment that requested 
it. However, if the request affects the work performed by an establishment under contract 
to the exempted establishment, the information about the exemption or alternative should 
be shared with the contract establishment. Note that a registered establishment could 
  10   
Contains Nonbinding Recommendations 
request an exemption or alternative that would apply to itself and a physically separate 
establishment (having different registration FDA Establishment Identifiers) under the 
same corporate management. 
 
An HCT/P that is the subject of an exemption or alternative request may be distributed to 
another establishment for utilization. The HCT/P must be distributed with the 
accompanying records required under  1271.155(f) (i.e., documentation of the grant of 
the exemption or alternative and the date on which you began operating under the terms 
of the exemption or alternative). 
 
 
V.  ESTABLISHMENT AND MAINTENANCE OF A QUALITY PROGRAM 
( 1271.160) 
 
A.  What is a Quality Program? 
 
Under  1271.3(hh), a quality program is an organizations comprehensive system for 
manufacturing and tracking HCT/Ps in accordance with 21 CFR Part 1271. 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. 
 
B.  Which Establishments Must Establish and Maintain a Quality Program? 
 
Any establishment that performs any step in the manufacture of HCT/Ps must establish 
and maintain a quality program that must be appropriate for the manufacturing steps 
performed and the specific HCT/Ps manufactured ( 1271.160(a)). Establish and 
maintain means to define, document (in writing or electronically), and implement; then 
follow, review, and as needed, revise on an ongoing basis ( 1271.3(cc)). For example, 
the quality program for a recovery establishment could include establishing and 
maintaining procedures to ensure that a donors relevant medical records, including the 
physical assessment, are complete. 
 
Each establishment has the flexibility to devise its own quality program, depending upon 
the functions it performs, and the HCT/Ps it manufactures. 
 
C.  What is the Role of the Quality Program Regarding Procedures? 
 
In addition to other requirements, under  1271.160(b)(1), the quality program must 
ensure that the establishment complies with the requirements for procedures relating to 
core CGTP requirements, and ensuring compliance with the requirements in  1271.180, 
with respect to such procedures, including review, approval and revision. 
  11   
Contains Nonbinding Recommendations 
 
D.  What Must I Do When Information is Received From Sources Outside the 
Establishment, and What Must I Do with this Information? 
 
The quality program must ensure that the establishment has procedures for receiving, 
investigating, evaluating, and documenting information relating to core CGTP 
requirements, including complaints ( 1271.160(b)(2)). You could receive this 
information before or after distribution of the HCT/P (e.g., complaints from the 
consignee or results of communicable disease tests performed by other establishments 
that recovered HCT/Ps from a shared donor). 
 
Example: An HCT/P establishment receives information from another establishment that 
a shared donor tested reactive for Hepatitis C Virus (HCV), with an FDA-licensed HCV 
nucleic acid test approved for cadaveric specimens. The establishment should investigate 
and evaluate the information received to determine if the HCT/P from this donor could 
potentially result in the transmission of a relevant communicable disease. The reactive 
test results for a relevant communicable disease agent or disease would mean that the 
donor is ineligible to donate ( 1271.80(d)(1)). In this case, the establishments quality 
program must ensure that procedures exist for all of the following: 
 
  the quarantine of any HCT/Ps in the establishments inventory from the same 
donor ( 1271.160(b)(2)(iii)). 
  the notification of all entities to whom the HCT/P was distributed 
( 1271.160(b)(2)(iii)). We recommend that this notification include written 
notification of the facts of the case (i.e., the reactive test results, the other 
establishments additional test results, and additional testing that will be or has 
been performed on archived specimens, and the results, when known). 
  the recall of the HCT/P, and/or reporting to FDA ( 1271.160(b)(2)(iii)) as 
necessary. 
 
In addition, we recommend that establishments instruct all consignees on procedures for 
return of unused HCT/Ps. 
 
E.  With Whom Must an Establishment Share Information Pertaining to the 
Possible Contamination of or Potential for Transmission of Communicable 
Disease by an HCT/P? 
 
Under  1271.160(b)(2), your quality program must ensure that procedures exist to share 
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: 
 
  other establishments that are known to have recovered HCT/Ps from the same 
donor ( 1271.160(b)(2)(i)); and 
  other establishments that are known to have performed manufacturing steps 
with respect to the same HCT/P ( 1271.160(b)(2)(ii)). 
  12   
Contains Nonbinding Recommendations 
We recommend that these procedures be defined in your contracts, agreements, and other 
arrangements with other establishments. 
 
Relating to consignees, in the case of such information received after the HCT/P has been 
made available for distribution, shipped to the consignee, or administered (implanted, 
transplanted, infused or transferred) to the recipient, procedures must include provisions 
for assessing risk and appropriate follow-up, 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 
( 1271.160(b)(2)(iii)). 
 
Example 1: An eye bank receives donor test results that are positive or reactive (even if 
that particular test is not recommended by FDA) for a relevant communicable disease. 
The eye bank evaluates this information and determines that this new information 
concerns a potential increase in the risk of communicable disease transmission by the 
HCT/P. The eye bank shares this information with the establishment, an organ 
procurement organization (OPO) that recovered organs and other HCT/Ps from the 
donor. The OPO must inform other establishments that received HCT/Ps from the same 
donor ( 1271.160(b)(2)(i)). The eye bank already has released the corneas, so it must 
notify its consignees ( 1271.160(b)(2)(iii)). 
 
Example 2: A recovery establishment has contracts with multiple processing 
establishments to recover HCT/Ps for them. When the recovery establishment receives 
information from one processing establishment that a recipient of an HCT/P from a 
shared donor had developed a serious infection related to the HCT/P, the recovery 
establishment is responsible for sharing this information with the other processing 
establishments that received HCT/Ps from the same donor ( 1271.160(b)(2)(iii)). 
 
F.  How Can a Quality Program Ensure that Appropriate Corrective Actions 
Related to Core CGTP Requirements Are Taken, When Necessary? 
 
The quality program must ensure that appropriate corrective actions relating to core 
CGTP requirements are taken and documented, as necessary ( 1271.160(b)(3)). The 
quality program must also verify that such corrective actions are effective and in 
compliance with CGTP requirements ( 1271.160(b)(3)). The corrective action should 
not adversely affect other operations. Where appropriate, corrective actions must include 
both short-term action to address the immediate problem, and long-term action to prevent 
the problems recurrence ( 1271.160(b)(3)). 
  13   
Contains Nonbinding Recommendations 
You must document (where appropriate) the following: 
 
  identification of the HCT/P affected and a description of its disposition 
( 1271.160(b)(3)(i)); 
  the nature of the problem requiring corrective action ( 1271.160(b)(3)(ii)); 
  a description of the corrective action taken ( 1271.160(b)(3)(iii)); and 
  the date(s) of the corrective action ( 1271.160(b)(3)(iv)). 
 
G.  What Must the Quality Program Ensure Regarding Personnel? 
 
The quality program must ensure that personnel involved in activities related to core 
CGTP requirements have proper training and education to perform those activities 
( 1271.160(b)(4)). 
 
Examples of how the quality program could ensure that personnel are properly trained 
and educated could include establishing training and education criteria for specific 
positions. This might be accomplished by ensuring that the content of training is relevant 
for an individual performing specific activities related to core CGTP requirements and by 
requiring a certain level of education and/or certification, as appropriate. For example, 
you may want to establish that: 
 
  personnel performing recoveries are certified by a professional organization; 
  individuals under contract, agreement, or other arrangement with your 
establishment that engage solely in recovering cells or tissues, who are exempt 
from registration but not from other applicable requirements ( 1271.15(f)), 
have proper training, education and/or experience as applicable to the 
recovery activities they perform; 
  donor eligibility determinations are performed by a responsible person who 
has the professional training to recognize risk factors for and clinical evidence 
of communicable disease agents by review of symptoms, signs and clinical 
laboratory results; and 
  personnel performing investigations of complaints or adverse reactions related 
to a possible communicable disease have the training and experience to 
review and interpret clinical records, including pathology reports, laboratory 
results and medical/surgical interventions. 
 
H.  How Does the Quality Program Ensure that Appropriate Monitoring 
Systems Are in Place? 
 
Under  1271.160(b)(5), your quality program must establish and maintain appropriate 
monitoring systems as necessary to comply with the requirements in Part 1271, Subpart 
D. For example, you might develop systems within the facility for environmental control 
( 1271.195(a)) (e.g., systems to monitor temperature and humidity), environmental 
monitoring ( 1271.195(c)) (e.g., viable particulate monitoring in a clean room), and 
storage ( 1271.260) (e.g., systems that monitor the temperature of HCT/P storage units 
and that would generate an alarm when out of range). 
  14   
Contains Nonbinding Recommendations 
 
I.  When HCT/P Deviations Occur, What is the Role of the Quality Program? 
 
Under  1271.160(b)(6), your quality program must investigate and document HCT/P 
deviations and trends of HCT/P deviations relating to core CGTP requirements and make 
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 ( 1271.160(b)(6)). 
 
Example: HCT/Ps are recovered, and the donor is determined to be eligible based on 
results of donor screening and testing. However, a later review of donor records 
determines that the donor was incorrectly determined to be eligible because the donor 
was not free from clinical evidence of infection due to relevant communicable disease 
agent or disease, as specified in your establishments SOPs. The recovered HCT/Ps are 
destroyed after processing and before distribution. This event is an HCT/P deviation 
related to core CGTP requirements that must be investigated and documented under 
 1271.160(b)(6), but it is not necessary to report the deviation to FDA under 
 1271.350(b), because the HCT/Ps were not distributed. 
 
J.  What Are the Requirements for Performing Quality Audits of Your 
Establishment? 
 
Under  1271.160(c), you must periodically perform for management review a quality 
audit of activities related to core CGTP requirements.  We recommend that a quality 
audit be conducted at least annually, and more frequently, if necessary. A quality audit 
is a documented, independent inspection and review of the establishments activities 
related to core CGTP requirements ( 1271.3(gg)). The quality audit verifies the degree 
of compliance with the core CGTP requirements, by examining and evaluating objective 
evidence ( 1271.3(gg)). We consider an inspection and review to be independent when 
it is performed by an individual who does not have direct responsibility for the matter 
being audited or is external to the audited establishment. 
 
K.  Will FDA Review the Quality Audit During Inspection of the Establishment? 
 
It is not our current policy to review or copy your actual quality audit reports during 
routine inspections and investigations except in certain limited circumstances (FDA 
Compliance Policy Guide (CPG) 130.300), (Ref. 4). However, you should have a 
mechanism to demonstrate to the FDA investigator that quality audits are performed. 
  15   
Contains Nonbinding Recommendations 
L.  If the Establishment Relies on Computer Software to Comply with Core 
CGTP Requirements, What Activities Must be Performed Before 
Implementing the Software? 
 
If the computer software is either custom software (designed specifically for you) or 
commercially available software that has been customized or programmed for you (e.g., 
to perform a user-defined calculation or create a table), you must validate the software for 
its intended use ( 1271.160(d)). If the computer software used to comply with core 
CGTP requirements has not been customized, but rather is off-the-shelf software that has 
not been modified, then you must verify the performance of the software for its intended 
use ( 1271.160(d)). You must approve and document these activities and results before 
implementation ( 1271.160(d)). If the software is being used for functions other than 
those related to core CGTP requirements, there is no requirement to either validate or 
verify. 
 
Validation means confirmation by examination and provision of objective evidence 
that particular requirements can consistently be fulfilled ( 1271.3(kk)), (e.g., a process 
consistently produces an HCT/P that meets its predetermined specifications). 
Verification means confirmation by examination and provision of objective evidence 
that specified requirements have been fulfilled ( 1271.3(ll)). 
 
Example 1: An establishment develops its own computer software to store information 
used to make donor eligibility determinations (a core CGTP requirement). The 
establishment must validate its software for this intended use ( 1271.160(d)). 
 
Example 2: An establishment uses a computer-generated labeling system, such as bar- 
coding, developed by a software company for a different intended use, such as labeling 
blood products. Since labeling controls ( 1271.250(a) and (b)) are core CGTP 
requirements, and the establishment is using the software for its own intended use, the 
establishment must validate the software for this intended use ( 1271.160(d)). You 
could refer to FDAs Guidance for Industry and FDA Staff entitled, General Principles 
of Software Validation dated January 2002 (Ref. 5). 
 
Example 3. An establishment uses a commercial electronic spreadsheet to record donor 
testing results which are used to make a donor eligibility determination. Since the 
software has not been modified, you must verify that it performs this activity correctly 
( 1271.160(d)). 
  16   
Contains Nonbinding Recommendations 
VI.  PERSONNEL ( 1271.170) 
 
A.  What Are the Specific Requirements for Personnel at HCT/P 
Establishments? 
 
You must have sufficient personnel to ensure compliance with the Part 1271 
requirements, and the personnel must have the necessary education, experience, and 
training to ensure competent performance of their assigned functions ( 1271.170(a) and 
(b)). You should determine the qualifications needed to perform manufacturing functions 
in your establishment(s) and should reflect these qualifications in a job/position 
description. In addition, personnel must perform only those activities for which they are 
qualified and authorized ( 1271.170(b)). You must train all personnel, and re-train as 
necessary, to perform their assigned responsibilities adequately ( 1271.170(c)). 
 
Example: Personnel performing recoveries, performing physical assessment of donors, 
or drawing blood specimens for communicable disease testing must be trained to perform 
their assigned activities (See  1271.170(b) and (c). As part of that training, personnel 
should be made aware of the possible consequences of improper performance of their 
activities, (e.g., the risk of transmission of communicable disease agents and diseases). 
An individual under contract agreement or other arrangement to a registered recovery 
establishment who performs only these functions and no other manufacturing steps does 
not have to register independently ( 1271.15(f)). 
 
B.  How Would I Ensure that Personnel Have the Necessary Education, 
Experience and Training to Perform Their Job? 
 
We recommend that you periodically review the qualifications, including training and 
professional development, of your personnel, not just when they are hired and initially 
trained, to ensure that they maintain skills necessary to perform their job. Some 
examples of evaluation tools you could use to ensure that your personnel have the 
necessary education, experience and training include: 
 
  developing criteria for each position and ensuring that personnel meet and 
continue to meet such criteria; and 
  setting up a program for demonstration of competency for their assigned 
functions when observed by a supervisor or appropriately experienced 
designee. 
 
 
VII.  PROCEDURES ( 1271.180) 
 
You must establish and maintain procedures appropriate to meet core CGTP requirements (listed 
in section III.A. of this guidance) for all steps that you perform in the manufacture of HCT/Ps 
( 1271.180(a)). 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 ( 1271.180(a)). 
  17   
Contains Nonbinding Recommendations 
 
A.  What Do I Need to do Before Implementing New Procedures Related to Core 
CGTP Requirements? 
 
Before implementation, you must have a responsible person review and approve new 
procedures ( 1271.180(b)). You must also ensure the periodic review and approval of 
procedures, and ensure compliance with the requirements of  1271.180 with respect to 
such procedures as a function of your quality program ( 1271.160(b)(1)). 
 
B.  Do Procedures Have to be Physically Maintained in the Area Where the 
Operation is Performed? 
 
Procedures must be readily available to personnel in the area where operations are 
performed ( 1271.180(c)). However, procedures do not have to be physically 
maintained in the area of operation if such availability is impractical ( 1271.180(c)). 
 
For example, copies (e.g., on paper, or electronic media) of recovery SOPs could travel to 
recovery sites with personnel or could be accessed electronically from a separate 
location, as long as they are easily accessible to all employees performing recovery. 
Also, for example, it may not be feasible to physically keep SOPs in clean rooms where 
processing operations occur, because the SOPs could cause contamination of HCT/Ps. In 
that case, you could keep the SOPs in an adjacent area outside the clean rooms. As long 
as a paper and/or electronic copy of the SOPs is physically available, additional methods 
of obtaining information, such as an immediate communication method using wired or 
wireless technologies from personnel with questions to personnel who have access to 
current procedures, could be used to resolve, answer or clarify questions that arise during 
operations. 
 
C.  May I Use Procedures From Established Industry Standards? 
 
Yes, provided that you verify that the procedures, whether followed in their entirety or if 
modified by your establishment, meet the requirements of Part 1271 and are appropriate 
for your operations ( 1271.180(d)). 
 
 
VIII.  FACILITIES ( 1271.190) 
 
A.  What Are General Requirements for HCT/P Facilities? 
 
Under  1271.190(a), 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 ( 1271.190(a)). 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. 
( 1271.190(a)). 
  18   
Contains Nonbinding Recommendations 
 
B.  What Facility Cleaning and Sanitation Issues Must I Consider? 
 
Under  1271.190(b)(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. You also must dispose of sewage, trash, and other 
refuse in a timely, safe, and sanitary manner ( 1271.190(b)(2)). 
 
We recommend that you have a cleaning program supported by environmental 
monitoring, where appropriate, as described in  1271.160(b)(5) and 1271.195(c). You 
should determine the appropriate frequency, method, and concentration of disinfectants to 
ensure prevention of contamination and cross-contamination in your facility. 
 
Example: You use a broad-spectrum disinfectant that has been demonstrated to 
inactivate bacteria and fungi on surfaces. You should follow the manufacturers 
instructions for proper dilution and adequate contact time and document that all 
parameters were met. 
 
C.  Is it Necessary to Perform Different Operations in Separate Areas Within a 
Facility? 
 
Under  1271.190(c), 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. 
 
It is not necessary that there be a separate designated room for each task performed 
during the manufacture of an HCT/P. You should evaluate the type of area that a task 
would require in order to prevent contamination or cross-contamination of HCT/Ps and 
designate an appropriate area for those tasks. 
 
For example, it would not be appropriate to utilize a clean room normally used for 
processing HCT/Ps to perform the following activities: 
 
  preparing packaged, recently recovered HCT/Ps for shipment to another 
facility; 
  prepackaging freshly recovered HCT/Ps for subsequent quarantine; 
  handling (e.g., centrifugation, serum/plasma separation) of blood specimens to 
be used for infectious disease testing; or 
  decontaminating instruments used for recovery or processing. 
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D.  What Facility-Related Procedures Must I Establish and Maintain? 
 
Sections 1271.190(a) and (b) requirements are core CGTP requirements 
( 1271.150(b)(1)). Therefore, you must establish and maintain procedures in accordance 
with  1271.180. In addition,  1271.190(d)(1) requires that you 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 ( 1271.190(d)(1)). 
 
E.  What Facility-Related Documentation Must I Maintain? 
 
In addition to the records required under  1271.270 (see section XIX of this guidance), 
 1271.190(d)(2) requires that you document, and maintain records of all cleaning and 
sanitation activities performed to prevent contamination of HCT/Ps. You should create 
these records concurrently with cleaning and sanitation activities. You must retain such 
records 3 years after their creation ( 1271.190(d)(2)). 
 
F.  How Do Facility-Related Requirements Apply to Recovery of HCT/Ps? 
 
The facility-related requirements apply to recovery of HCT/Ps. You should determine 
how to evaluate an area used for recovery in order to prevent contamination and cross- 
contamination, according to the general facilities requirements under  1271.190(a). As 
these recovery facilities may not be under your day-to-day control, you should establish 
and maintain procedures to prevent the introduction, transmission, or spread of 
communicable disease that may be implemented during each recovery. You should 
consider the following issues when evaluating an area used for recovery: 
 
  Does the facility offers a suitable size, location, and is constructed so that an 
aseptic recovery can be successfully performed; 
  Is there limited access to the recovery site during recovery; 
  Is the site in a good state of repair; 
  Is there adequate lighting and space; 
  Are ventilation and airflow adequate (e.g., no open windows, vent is not 
located directly above the recovery operations); 
  Is there access to a sink; 
  Are all working surfaces used for the recovery operations cleaned with 
verified cleaning agent and the cleaning documented before recovery; and 
  Can aseptic technique be adequately performed. 
 
A description and/or a checklist could be used to document that the recovery site meets 
established, desired parameters each time a recovery is performed. The site of the 
recovery should be documented. Before entering into a contract with a recovery 
establishment, a processor could examine the facilities where recoveries take place. 
  20   
Contains Nonbinding Recommendations 
IX.  ENVIRONMENTAL CONTROL AND MONITORING ( 1271.195) 
 
A.  What Environmental Controls Must I Have in Place at My Facility? 
 
Under  1271.195(a), 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: 
 
  temperature and humidity controls ( 1271.195(a)(1)); 
  ventilation and air filtration ( 1271.195(a)(2)); 
  cleaning and disinfecting of rooms and equipment to ensure aseptic processing 
operations ( 1271.195(a)(3)); and 
  maintaining equipment used to control conditions necessary for aseptic 
processing operations ( 1271.195(a)(4)). 
 
We are not recommending clean room classification requirements for particular facilities 
or manufacturing steps. You should determine the appropriate level of control. The 
appropriate level of control may depend on such factors as which manufacturing steps are 
involved, whether they are performed in an open or closed system, whether they are 
performed in a laminar flow hood (LFH) or biological safety cabinet (BSC), and other 
factors as described in the FDA guidance entitled Guidance for Industry: Sterile Drug 
Products Produced by Aseptic Processing  Current Good Manufacturing Practice dated 
September 2004 (Ref. 6). This guidance could provide useful information to an HCT/P 
establishment that is developing procedures on environmental control and monitoring. 
Also, chapter <1116> Microbiological Evaluation of Clean Rooms and Other Controlled 
Environments in US Pharmacopoeia 30 (Ref. 7) contains information on environmental 
monitoring. 
 
We recommend that you determine the types of microorganisms that could exist in your 
facility, and design your cleaning and environmental control and monitoring programs 
accordingly. You should select the types of disinfectant/cleaning agents to use that are 
effective against microorganisms you have identified. 
 
Example: An eye bank recovers whole globes. We recommend that processing (i.e., 
removal of the cornea from the whole globe) be performed in a LFH or BSC because this 
equipment provides a controlled environment and can be adequately cleaned and 
monitored. 
 
B.  How Often Must I Inspect My Environmental Control Systems? 
 
Under  1271.195(b), 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 ( 1271.195(b)). 
  21   
Contains Nonbinding Recommendations 
C.  Is Environmental Monitoring Required? 
 
Under  1271.195(c), 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 ( 1271.195(c)). 
 
For example, we recommend that you perform periodic monitoring of non-viable and 
viable particulates, work surfaces, and personnel. This monitoring should be performed 
in clean rooms using LFHs and BSCs for processing in order to evaluate environmental 
changes that may increase the likelihood of contamination or cross-contamination of 
HCT/Ps. 
 
D.  What Temperature and Humidity Factors Should be Considered for 
Environmental Control and Monitoring? 
 
Each establishment has the flexibility to determine if temperature and humidity could 
reasonably be expected to have an adverse effect on the HCT/Ps it manufactures. For 
example, if steps in the manufacture of HCT/Ps have identifiable parameters for 
maintaining a certain temperature and/or humidity, or the performance of the reagents 
used in the manufacturing of HCT/Ps could be adversely affected by temperature and/or 
humidity over the length of storage of the reagent or product, you must adequately 
control and monitor environmental conditions and provide proper conditions for 
operations (see  1271.195(a) and (c)). 
 
E.  How Often Should I Perform Environmental Monitoring? 
 
Under  1271.195(c), 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. Under  1271.195(b), you must inspect each environmental control system 
periodically to verify that the system, including necessary equipment, is adequate and 
functioning properly. You have the flexibility to design your environmental monitoring 
system for the type of operations and particular environmental factors in your facility. 
 
We recommend that you define the type and frequency of environmental monitoring to 
be performed, including the monitoring used to verify that cleaning procedures are 
adequate, and that the environmental control systems are capable of maintaining the 
degree of control specified. We recommend that you define alert and action levels for 
test results and specify potential corrective actions when alert and/or action levels are 
exceeded. The following types of environmental monitoring should be considered in 
clean rooms, LFHs, and BSCs used for processing: 
 
  non-viable particulate air monitoring; 
  viable particulate air monitoring; 
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Contains Nonbinding Recommendations 
  clean area positive pressure levels; 
  surface monitoring (taking into account all different surfaces in the 
manufacturing environment); and 
  personnel monitoring (e.g., touch plates). 
 
F.  Are records related to environmental control and monitoring required? 
 
You must document and maintain records of environmental control and monitoring 
activities under  1271.195(d). In addition, under  1271.270, you must retain records 
concurrently with the performance of each step required in Part 1271, Subparts C and D, 
including the environmental control and monitoring activities required under 
 1271.195(a) through (c). We also note that the requirements for environmental control 
under  1271.195(a) are core CGTP requirements ( 1271.150(b)(2)). 
 
G.  What Procedures Related to Environmental Control and Monitoring Must I 
Establish and Maintain? 
 
Requirements related to environmental control in  1271.195(a) are core CGTP 
requirements ( 1271.150(b)(2)). Therefore, you must establish and maintain procedures 
in accordance with  1271.180. The regulations do not set forth specific procedures for 
environmental monitoring. However, for environmental monitoring that you conduct in 
accordance with  1271.195(c), we recommend that you specify the type and frequency 
of environmental monitoring, define alert and action levels for test results, and specify 
potential corrective actions when alert and/or action levels are exceeded (see section 
IX.E.). 
 
H.  What Environmental Control and Monitoring Issues Should be Considered 
for Recovery of HCT/Ps? 
 
Environmental control and monitoring considerations during recovery operations are 
similar to those of other manufacturing steps. You must consider the need for 
environmental control and monitoring of facilities used for HCT/P recovery (see 
 1271.195(a) and (c)). Requirements relating to recovery in  1271.215 are core CGTP 
requirements ( 1271.150(b)(5)). Therefore, you must establish and maintain procedures 
in accordance with  1271.180 to prevent contamination or cross-contamination during 
recovery, or circumstances that otherwise increase the risk of the introduction, 
transmission or spread of communicable disease through the use of the HCT/P. While 
environmental monitoring might not have to be performed at each recovery site, you must 
have controls in place to provide assurance that the site of recovery does not increase the 
potential for contamination and cross-contamination of HCT/Ps (see  1271.195). You 
should set specific parameters for recovery site suitability and verify for each recovery 
that these parameters have been met. A controlled environment, such as an operating 
room setting, is recommended but not required. If other types of facilities are used for 
recovery, adequate temperature and humidity controls, and adequate ventilation and air 
filtration must be provided where appropriate ( 1271.195(a)(1) and (2)). 
  23   
Contains Nonbinding Recommendations 
Information regarding recovery sites for dura mater can be found in the document entitled 
Guidance for Industry and FDA Staff, Class II Special Controls: Guidance Document: 
Human Dura Mater, in section 10: Manufacturing Controls, Part B. Excision Facilities 
(Ref. 8). Specifically, in that guidance we recommend that the recovery site meet the 
standards of a surgical operating room at a minimum. 
 
This guidance recommends that recovery sites should have: 
 
  air filtration; 
  stainless steel furniture; 
  washable walls; 
  refrigeration for donor storage; 
  hypothermia blankets to cool the donor during the procedure; and 
  single use or disposable instruments for each donor. 
 
X.  EQUIPMENT ( 1271.200) 
 
A.  What Are the General Equipment Requirements? 
 
Under  1271.200(a), equipment used in the manufacture of HCT/Ps must be of 
appropriate design for use and must be suitably located and installed to facilitate 
operations, including cleaning and maintenance, in order to prevent the introduction, 
transmission, or spread of communicable diseases. Any automated, mechanical, 
electronic, or other equipment used for inspection, measuring, or testing in accordance 
with Part 1271 must be capable of producing valid results ( 1271.200(a)). You must 
clean, sanitize, and maintain equipment according to established schedules 
( 1271.200(a)). You should consider the equipment's potential to influence 
contamination and cross-contamination of HCT/Ps during use. We recommend you 
develop and execute an installation plan for equipment, if applicable, to ensure that the 
equipment is suitably located and installed (in accordance with the equipment 
manufacturers specified requirements) and operates properly. 
 
B.  Do I Have to Qualify or Certify Equipment (Installation Qualification, 
Operational Qualification, Performance Qualification)? 
 
Equipment qualification and certification are well established methods for ensuring that 
equipment can operate and produce desired results consistently. While  1271.200 does 
not explicitly require equipment qualification and certification, it is long-standing 
industry standard practice to do so, particularly as part of process validation (See FDA 
guidance entitled Process Validation: General Principles and Practices dated January 
2011 (Ref. 9), which also may be useful to consider). We recommend that you qualify 
and certify your equipment. You should routinely perform certification for certain 
equipment such as LFHs and BSCs, according to the manufacturers specifications. 
  24   
Contains Nonbinding Recommendations 
Example: A LFH is generally certified when initially installed. Periodic recertification 
to ensure that the LFH is operating as intended could include measuring the air flow and 
velocity, ensuring proper operation of the high efficiency particulate air (HEPA) filter 
(e.g., particle testing), and/or making sure that the exhaust is properly directed. An event 
or activity that warrants recertification of the LFH would include, but is not limited to, 
repair or replacement of parts. 
 
C.  Does Recovery Equipment (e.g., Instruments) Have to be Segregated by 
Donor Prior to Cleaning in an Automated Washer? 
 
You are not required to segregate recovery equipment used for different donors prior to 
cleaning in an automated washer. It is acceptable to place multiple instrument trays into 
the same automated washers. If possible, it would be preferable to clean instruments 
used on the same type of tissue together in such loads (such as those used for 
musculoskeletal HCT/P recovery). You should ensure that automated washers operate 
consistently and that they are properly cleaned after each use, according to established 
procedures. 
 
D.  Is There Any Prohibition on the Re-Use of Cleaning/Disinfection Solutions, 
or Containers Used to Clean and Disinfect Instruments? 
 
As long as the manufacturers instructions for use of cleaning/disinfection solutions allow 
for reuse, then it is acceptable to reuse such solutions. For most of these 
cleaning/disinfection solutions, the manufacturers instructions give information about 
how frequently to change the solutions, varying from daily to weekly and/or when 
visually unsuitable. Containers used in instrument cleaning could also be reused as long 
as they are cleaned and sanitized after each use. 
 
E.  Are There Special Considerations for Cleaning and Sanitizing Equipment at 
Risk for Transmissible Spongiform Encephalopathy Contamination? 
 
While prion contamination is a significant concern, existing technology and current 
scientific information is limited regarding reducing the risk of transmissible spongiform 
encephalopathy (TSE) in surgical instruments used for HCT/P recovery and/or 
processing. There are neither definitive recommendations for how to reliably perform 
TSE decontamination, nor procedures for rapidly identifying the presence of prions on 
instruments. However, we recommend that you use heightened screening and stringent 
recovery procedures. For example, where possible, consider using disposable 
instruments for recovery of HCT/Ps at high-risk for prion contamination, such as cornea 
and dura mater. You should consider establishing procedures to track instruments that 
were used on particular donors as well as instruments that are cleaned and sanitized 
together. FDAs Transmissible Spongiform Encephalopathies Advisory Committee 
advised on July 18, 2003, that instruments need not routinely undergo special cleaning 
procedures prior to sterilization, even if these instruments were used to recover or process 
high-risk HCT/Ps (Ref. 10). However, if a particular donor after recovery was found to 
  25   
Contains Nonbinding Recommendations 
have or was suspected of having a TSE, then the instruments used for recovery should be 
destroyed. You must keep records of the instruments used in the recovery and/or 
processing of a donors HCT/Ps (see  1271.200(e) and 1271.270(a)). 
 
F.  What Procedures and Schedules Are Required for Equipment? 
 
Section 1271.200(a) requirements are core CGTP requirements ( 1271.150(b)(3)). 
Therefore, you must establish and maintain procedures in accordance with  1271.180. 
Under  1271.200(b), 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. 
 
We do not specify cleaning schedules for equipment. Each establishment has the 
flexibility to determine and justify cleaning procedures that will prevent the introduction, 
transmission or spread of communicable diseases. Manufacturers instructions for 
cleaning materials and equipment could provide useful information for determining 
appropriate cleaning schedules for your equipment. 
 
For example, apheresis machines using disposable tubing may not require cleaning 
between each HCT/P recovery. However, if there is a spill, there should be special 
cleaning procedures in place. 
 
G.  What Equipment Calibration Must I Perform? 
 
Under  1271.200(c), 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. For example, an instrument used 
to monitor the temperature of an HCT/P storage unit must be regularly calibrated. Some 
equipment, such as computers, are not subject to calibration. 
 
In order to determine an appropriate calibration schedule, you could consult the 
Operations Manual or contact the manufacturer of the equipment to determine and 
establish appropriate intervals for calibrating each piece of equipment. You should also 
take into consideration the specific use of this equipment within the manufacturing 
facility to determine if special conditions could warrant more frequent calibration than is 
recommended by the equipment manufacturer. Calibration accuracy should be traceable 
to accepted/known standards (e.g., National Institute of Standards and Technology, 
http://www.nist.gov/), or the manufacturers supplied or recommended standard. 
 
H.  What Equipment Inspections Must I Perform? 
 
Under  1271.200(d), you must routinely inspect equipment for cleanliness, sanitation, 
and calibration, and to ensure adherence to applicable equipment maintenance schedules. 
  26   
Contains Nonbinding Recommendations 
I.  What Records Related to Equipment Must I Keep? 
 
Under  1271.200(e), you must document and maintain records of all equipment 
maintenance, cleaning, sanitizing, calibration, and other activities performed in 
accordance with  1271.200. 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 ( 1271.200(e)). You must maintain records of 
the use of each piece of equipment, including the identification of each HCT/P 
manufactured with that equipment ( 1271.200(e)). You must keep records for cleaning 
and maintenance of equipment (including simple instruments that are regularly washed 
and disinfected), tools, and other equipment used or reused in the manufacturing of 
HCT/Ps to document that the items were adequately cleaned and maintained in order to 
prevent their contamination or cross-contamination by communicable disease agents 
(1271.200(e)). 
 
For example, for single-use instruments, you must maintain records of the use of that 
equipment, including the identification of each HCT/P manufactured with that equipment 
( 1271.200(e)). Maintaining records for the use of single-use instruments would be 
helpful, for example, to the HCT/P manufacturer in case the single-use device is recalled 
because the manufacturer discovered that the distributed devices were not sterile. 
 
If it is necessary to implement an alternate method of identifying the current 
maintenance, cleaning, sanitizing and/or calibration status of each piece of equipment, the 
alternate method should permit the operator to easily check, prior to each use, that the 
equipments maintenance, cleaning, sanitizing and/or calibration have been properly 
performed. 
 
You may have another establishment perform equipment maintenance, cleaning, 
sanitizing, and/or calibration for you, under a contract, agreement or other arrangement. 
You may use the other establishments records to demonstrate compliance with 
 1271.200. However, you are still responsible for ensuring that the services provided 
are adequate and in compliance with applicable requirements (See  1271.150(c)(1)(ii) 
and (iii)). 
 
See section XIX of this guidance ( 1271.270) for further information about general 
recordkeeping requirements. 
 
J.  What Are the Responsibilties of Recovery Establishments that Contract the 
Cleaning and Sterilization of Recovery Instruments (Equipment)? 
 
In order to demonstrate that cleaning and sterilization of recovery instruments performed 
by a contract facility are appropriate, the recovery establishment should: 
  obtain and approve the procedures, and review the records of cleaning and 
sterilization per  1271.200; 
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Contains Nonbinding Recommendations 
  establish and maintain verification procedures under  1271.210 for any 
instruments cleaned and sterilized for you by a facility under contract, 
agreement or other arrangement; and 
  have the procedures and records available for review on inspection. 
 
Establishments that only clean and sterilize recovery instruments (equipment) under 
contract, agreement, or other arrangement to a registered recovery establishment are not 
required to register, because this function is not considered a manufacturing step. 
 
 
XI.  SUPPLIES AND REAGENTS ( 1271.210) 
 
A.  What Are Supplies and Reagents? 
 
Supplies and reagents include all materials that are used during manufacture, not just 
those coming into direct contact with HCT/Ps. Examples of supplies include sterile 
drapes, gauze, cleaning swabs, alcohol pads, and instruments (equipment) that are 
cleaned and sterilized under contract, agreement or other arrangement for you. Examples 
of reagents include cleaning agents, saline, dimethyl sulfoxide, anticoagulants, and 
chemical and antibiotic solutions used in processing. 
 
B.  What Verification is Required for Supplies and Reagents? 
 
Under  1271.210(a), 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 ( 1271.210(a)). Use of a contaminated or otherwise defective supply 
or reagent in the manufacture of an HCT/P could lead to such problems as the 
introduction of a communicable disease agent or the failure to properly preserve the 
HCT/P. 
 
You or a vendor must verify that those supplies and reagents used in all steps of the 
manufacture of HCT/Ps (not only those that come in contact with an HCT/P), including 
recovery, meet specifications designed to prevent circumstances that increase the risk of 
introduction, transmission, or spread of communicable diseases (see  1271.210(a) and 
(b)). You should store and use supplies and reagents according to the manufacturers 
instructions. We recommend that you keep product information data sheets for all 
supplies and reagents used, update these sheets as products change, and keep an archive 
of previously used products. Verification that reagents meet specifications may be 
accomplished either by reviewing the Certificate of Analysis (COA) or by performing 
relevant testing. For supplies such as sterile drapes or gloves that are not expected to 
have a COA, we recommend that you obtain information from the vendor on the relevant 
specifications and the manufacturing of the supply. You must maintain records of the 
verification of each supply or reagent, including test results or, in the case of vendor 
verification, a COA from the vendor ( 1271.210(d)(2)). 
  28   
Contains Nonbinding Recommendations 
 
C.  What Are Some Methods to Verify Reagents or Supplies? 
 
If you receive supplies and/or reagents from a vendor or another establishment, you 
should verify that the vendor or other establishment has a system in place to certify that 
the supplies and/or reagents meet established specifications. You could reference 
specification sheets, COAs, and manufacturers package inserts describing the reagent 
and/or supply to verify suitability. 
 
If a processor requires that specific supplies and reagents be used by recovery 
establishments, then the processor should verify the supplies and reagents and should 
include this information in its contracts, agreements, or other arrangements with the 
recovery establishment. 
 
Example: Supplies used to wrap or package the individual HCT/Ps at recovery should be 
designed to prevent leakage that could cause contamination or cross-contamination, and 
should be able to perform in this capacity when subjected to expected storage 
temperatures for that HCT/P type. 
 
D.  Are Reagents Required to be Sterile? 
 
Under  1271.210(b), reagents used in processing and preserving HCT/Ps must be sterile, 
where appropriate. 
 
Example: Non-sterile water might be appropriate for use during processing prior to 
terminal sterilization of the HCT/P, if the water meets specifications for use determined 
during process validation. 
 
E.  What is Required of Reagents I Produce In-House? 
 
You must validate and/or verify the processes used for production of in-house reagents 
( 1271.210(c)). For example, in the case of reagents produced for disinfecting recovery 
processes, the recovery establishment must verify that these reagents meet specifications 
designed to prevent circumstances that increase the risk of the introduction, transmission 
or spread of communicable diseases (e.g., solutions are sterile, where appropriate, have 
the proper concentrations, and fall within a specific pH range). (See  1271.210(a) 
through (c)). 
 
F.  What Records Must I Keep Related to Supplies and Reagents? 
 
Under  1271.210(d), you must maintain the following records pertaining to supplies and 
reagents: 
 
  records of the receipt of each supply or reagent, including the type, quantity, 
manufacturer, lot number, date of receipt, and expiration date; 
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Contains Nonbinding Recommendations 
  records of the verification of each supply or reagent, including test results or, 
in the case of vendor verification, a COA from the vendor; and 
  records of the lot of supply or reagent used in the manufacture of each HCT/P. 
 
You should establish a system under which particular lots of supplies and reagents can be 
linked to individual HCT/Ps. This does not necessarily require an individual record for 
each supply used in preparing every HCT/P (e.g., sterile drapes and gloves).  For 
instance, you may track those supplies by recording dates between which certain lot 
numbers were used, rather than individually recording each supply as it is used during the 
manufacture of each HCT/P. Maintaining the records required in  1271.210(d)(3) will 
enable you to determine which lots of supplies and reagents were used at a particular time 
and which HCT/Ps were manufactured during that same time period. This would 
facilitate a recall of HCT/Ps if the supplies or reagents used in their manufacture are later 
found to increase the risk of introduction, transmission, or spread of communicable 
diseases. 
 
G.  What Procedures Related to Supplies and Reagents Must I Establish and 
Maintain? 
 
Section 1271.210(a) and (b) requirements are core CGTP requirements 
( 1271.150(b)(4)). Therefore, you must establish and maintain procedures in accordance 
with  1271.180. 
 
 
XII.  RECOVERY ( 1271.215) 
 
Recovery means obtaining from a human donor cells or tissues that are intended for use in 
human implantation, transplantation, infusion, or transfer ( 1271.3(ii)). 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 
( 1271.215). 
 
In general, establishments that recover HCT/Ps must register with FDA ( 1271.10(b) and 
1271.20). However, if you, the registered establishment, contract with or have an agreement or 
other arrangement with an individual to recover tissue (e.g., ocular tissue) or cells (e.g., cord 
blood)) for you and send the HCT/P to you for processing, that individual does not have to 
register or list independently. That individual must comply with all other applicable 
requirements in Part 1271 ( 1271.15(f)). 
 
A.  What Procedures and Records Related to Recovery Are Required? 
 
Section 1271.215 requirements are core CGTP requirements ( 1271.150(b)(5)). 
Therefore, you must establish and maintain procedures in accordance with  1271.180. 
You must also establish and maintain procedures for other core CGTP requirements 
related to recovery operations where appropriate, such as: 
  30   
Contains Nonbinding Recommendations 
 
  facilities ( 1271.190(a) and (b)); 
  environmental control ( 1271.195(a)); 
  equipment ( 1271.200(a)); 
  supplies and reagents (1271. 210(a) and (b)); 
  labeling controls (1271.250(a) and (b)); 
  storage ( 1271.260(a) through (d)); and 
  receipt, predistribution shipment, and distribution of an HCT/P 
( 1271.265(a) through (d)). 
 
Your quality program must address all of these core CGTP requirements ( 1271.160(b)). 
Maintenance of records and a record management system must be in compliance with 
 1271.270. 
 
B.  What Are Some Ways that a Recovery Establishment Could Ensure that 
HCT/Ps Are Recovered 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? 
 
You should evaluate all recovery-related operations to determine how these activities can 
be performed to control contamination and cross-contamination, including the following: 
 
  technical procedures used; 
  personnel involved; 
  equipment, supplies, and reagents that are used during recovery; and 
  facilities where recoveries take place (See section VIII. F. of this guidance). 
 
Examples include: 
 
  Staff must have the experience, education and training necessary to perform 
recovery operations (see  1271.170). 
  Recovery site suitability parameters must be established and documented, 
including facility cleaning and maintenance, and environmental controls 
(see  1271.190 and 1271.195). 
  Specific body cooling parameters including time and temperature limits for 
recovery should be established. For example current tissue industry standards 
recommend that the time limit for tissue recovery should not exceed: 
  24 hours after death if the body is cooled or refrigerated within 12 
o
hours of death; or 
  15 hours after death if the body was not cooled or refrigerated. 
o
  Recovery should be performed using aseptic technique. 
  Recognized, published industry practices appropriate to controlling 
contamination (e.g., zone recovery, isolation draping, sequencing) should be 
utilized. 
  31   
Contains Nonbinding Recommendations 
  HCT/Ps should not be recovered from an area of the body where there is 
localized infection. 
  Equipment used in the manufacture of HCT/Ps must be of appropriate design 
for its use ( 1271.200(a)); we consider equipment to include instruments. 
You must clean, sanitize, and maintain equipment according to established 
schedules ( 1271.200(a)). You must document and maintain records of all 
equipment maintenance, cleaning, sanitizing, calibration, and other activities 
performed in accordance with  1271.200 ( 1271.200(e)). 
  Supplies and reagents used during recovery must be in compliance with 
 1271.210(a) through (c) and records must be maintained in compliance with 
 1271.210(d). 
  Recovery activities and problems related to microbial contamination should 
be evaluated (e.g., technical errors, pre-processing culture results should be 
tracked and trended). 
 
C.  What Are Ways in Which a Recovery Establishment Could Identify the 
Donor Prior to HCT/P Recovery? 
 
Verifying and documenting the donor identity is the first step in HCT/P tracking and is 
critical for preventing the spread of communicable disease agents or diseases by ensuring 
that donor eligibility information corresponds to the actual donor of the HCT/Ps (see 
 1271.270(a)). Prior to recovering HCT/Ps from a deceased donor, you should compare 
the potential donors identification with the donors name as stated on the 
consent/authorization document and relevant medical records, and compare other 
identifiers such as age, sex, race, and weight. 
 
You should ask living donors to verify their name prior to HCT/P collection. You should 
document the methods used to verify the donor identity and should include the source of 
the verification information (e.g., photo ID such as a drivers license, hospital ID tag or 
band, identification by appropriate recovery site personnel, living donors statement of 
his/her name), the date and time at which the identification was made, and the name of 
the recovery staff member(s) who made the identification. For deceased donors, you 
could reproduce the donors identification tag or band by photographing it, thereby 
documenting its content, or manually reproduce the contents of the identification method 
using a standardized form. 
 
D.  What Are Ways in Which a Processor Receiving HCT/Ps From a Recovery 
Establishment Under Contract with the Processor Could Verify the Identity 
of the Donor and Could Ensure That the Donor Records Are From the Same 
Donor as the HCT/Ps? 
 
A processor could periodically audit the records provided by the recovery establishment 
by comparing them to other publicly available information related to the donors and/or 
could contact the physicians referenced in the donor records. 
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XIII.  PROCESSING AND PROCESS CONTROLS ( 1271.220) 
 
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 
( 1271.220(a)). 
 
A.  What is Processing? 
 
Under  1271.3(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. 
 
In the context of this guidance, the set of processing activities that an establishment 
performs on an HCT/P taken together would be considered a process and would be 
subject to regulations such as  1271.220, 1271.225, and 1271.230. 
 
Example 1:  Corneal processing could include separation of the corneoscleral rim from 
the globe following enucleation (removal of the eye), cutting of corneas in preparation for 
Endothelial Keratoplasty (EK) procedures, microbiological culture of the rim, and 
placement of the cornea in a vial containing storage/transport media. If the cornea is 
recovered in situ and placed directly in the storage media with no further preparation, we 
would not consider that processing. 
 
Example 2: Processing of cell products could include red cell or plasma removal, cell 
selection, and cryopreservation for long-term storage. 
 
Example 3: Heart valve processing could include dissection and sizing of the aortic and 
pulmonic valves, antibiotic treatment, and cryopreservation. 
 
Example 4: Processing steps for musculoskeletal HCT/Ps could include removal of 
blood and lipids through chemical or physical means, various chemical and/or antibiotic 
soaks and washes, machined shaping of the bone, and the use of gamma irradiation as a 
bioburden reduction or terminal sterilization method. 
 
Processing also includes obtaining specimens that are subsequently sent for 
microbiological testing (e.g., collection of swab specimens or representative HCT/Ps for 
destructive cultures), and the actual microbiological testing, including speciation of 
microorganisms that are detected. 
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B.  May I Pool HCT/Ps? 
 
1.  Pooling HCT/Ps from two or more donors 
 
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 
( 1271.220(b)). For example, commingling bones from different donors during 
processing would be considered pooling. Pooling does not include the sequential 
transplantation of HCT/Ps (e.g., bone, skin) from different donors or the 
sequential administration of cellular products (e.g., cord blood) from different 
donors. In the event that you determine that pooling of HCT/Ps from two or more 
donors is necessary to obtain a therapeutic dose, you may request an exemption or 
alternative under  1271.155. 
 
2.  Pooling HCT/Ps recovered at different times from one donor 
 
In general, we discourage the practice of pooling cellular products that were 
collected from a single donor at different points in time during processing or post- 
thaw because of the increased risk that one product could be contaminated and 
could cross-contaminate the other. However,  1271.220(b) does not prohibit the 
practice of pooling cellular products that were collected from a single donor as 
long as the processing otherwise complies with the applicable requirements and 
the tracking/labeling systems are well-controlled in order to prevent mix-ups. 
 
C.  What in-Process Control and Testing Must I Perform? 
 
Under  1271.220(c), you must ensure that specified requirements, consistent with the 
general requirements of  1271.220(a), 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 until necessary approvals are received and 
documented. Sampling of in-process HCT/Ps must be representative of the material to be 
evaluated ( 1271.220(c)). 
 
You should establish appropriate, objective mechanisms to control and monitor each 
process to ensure that you are processing HCT/Ps 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. You could use a variety of methods for controlling and monitoring your 
processes including, statistical process-control methods, review of product acceptance 
criteria and results, as well as a meaningful quality audit. 
 
Section 1271.220(c) requires in-process control and testing. To be in compliance with 
this section you could check the results of testing at various steps in processing (for 
example, by sampling in-process HCT/Ps). The sample selected for testing (e.g., culture) 
must be representative of the HCT/P to be evaluated ( 1271.220(c)). This may not be 
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the case if a small portion of a large musculoskeletal HCT/P or companion HCT/P (i.e., 
HCT/Ps adjacent to the HCT/P that is processed along with the HCT/P) is cultured. In a 
March 15, 2002, Morbidity and Mortality Weekly Report, the Centers for Disease 
Control and Prevention (CDC) recommended that you consider performing both 
destructive and swab cultures of musculoskeletal HCT/Ps (Ref. 11). 
 
D.  Why Are Pre-Processing (Microbiological) Cultures Important? 
 
Section 1271.220(c) requires in-process control and testing. We believe that pre- 
processing cultures (sometimes referred to as pre-disinfection cultures) for 
musculoskeletal HCT/Ps (e.g., bone, tendon, ligament) should be performed because they 
are a critical in-process control. We further recommend that all results for pre-processing 
cultures from a particular donor should be considered when determining whether to 
accept or reject incoming musculoskeletal HCT/Ps from that donor prior to processing. 
Based on our Tissue Safety Teams8 investigations of adverse reaction reports related to 
transmission of communicable disease by musculoskeletal HCT/Ps, we recommend 
processors properly assess and utilize the results of pre-processing cultures. 
 
A disinfection or sterilization process must be validated based on the capability of that 
process to reduce or eliminate an expected level and mix of microorganisms on the 
particular products that will be put through the process. Thus, if musculoskeletal HCT/Ps 
are processed with bioburden in excess of the level that the process has been validated to 
remove or inactivate (e.g., multiple pre-processing cultures from a single donor are 
positive for enteric or pathogenic microorganisms, or are positive for microorganisms 
that have proved most difficult to reduce or eliminate, such as Clostridium or 
Streptococcus pyogenes (group A strep)), there is no assurance that the process will result 
in the reduction or removal of bioburden to acceptable limits or reduce the risk of 
transmission of communicable disease. 
 
Pre-processing cultures play a critical role in monitoring the process input to ensure that 
the process capability will not be affected. However, as discussed during the October 11- 
12, 2007, FDA/CDC workshop entitled, Processing Methods for Orthopedic, 
Cardiovascular, and Skin Allografts,9 and acknowledged in section 5.4.1 of the 
Association for the Advancement of Medical Instrumentation (AAMI)s new technical 
information report (TIR37:2007),10 current microbiological testing methodologies 
present unique challenges that can be difficult to overcome. In particular, current 
methods for sampling HCT/Ps are limited. Furthermore, certain microorganisms are 
difficult to 
 
8 The Tissue Safety Team consists of CBER representatives from several Offices and the primary purpose is to 
provide a coordinated process for the review, investigation and communication of reports of HCT/P adverse 
reactions. 
9 Transcript available at 
http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/Transcripts 
Minutes/UCM054425.pdf 
10 The referenced document is an AAMI technical information report (TIR37:2007), entitled Sterilization of health 
care products  Radiation  Guidance on sterilization of human tissue-based products, which published on 
November 20, 2007. The document is available at http://www.aami.org. 
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culture, so if they are present on/in an HCT/P at low levels, testing may not detect them. 
Thus, even when working with a validated process, processors should bear these 
limitations in mind as they plan pre-processing cultures and as they assess the results. 
 
We recommend that for all HCT/Ps, you: 
 
  Carefully consider the capability of your microbiological testing, disinfection, 
and sterilization processes when you evaluate pre-processing cultures to 
determine whether or not the HCT/Ps should be processed. 
 
We further recommend that for musculoskeletal HCT/Ps, you: 
 
  Discard all musculoskeletal HCT/Ps from a donor that has any 
musculoskeletal pre-processing cultures positive for Clostridium, 
Streptococcus pyogenes (group A strep), or any other microorganisms that 
you have determined to be difficult to eliminate, unless you have a terminal 
sterilization process validated to a sterility assurance level (SAL) of 10-6. 
 
  Discard all musculoskeletal HCT/Ps from a donor who has multiple 
musculoskeletal pre-processing cultures positive for enteric or pathogenic 
microorganisms, unless you have a terminal sterilization process validated to a 
SAL of 10-6. 
 
E.  Are HCT/Ps Required to be Sterile? 
 
We do not require that HCT/Ps be sterile, but you should use aseptic technique during 
manufacturing to prevent contamination and cross-contamination. It is the current 
industry practice to use aseptic technique during recovery and processing. Each step used 
in the processing of HCT/Ps must be controlled to prevent the introduction, transmission, 
or spread of communicable disease agents (see  1271.220(a)). 
 
F.  What Special Processing and Process-Control Considerations Must I Have 
for Dura Mater? 
 
For dura mater, when there is a published validated process that reduces the risk of TSE, 
you must use this process (or an equivalent process that you have validated), unless this 
process adversely affects the clinical utility of the dura mater ( 1271.220(d)(1)). 
Furthermore, when you use a published validated process, you must verify such a process 
in your establishment ( 1271.220(d)(2)). 
 
We realize that validated methods for reducing TSE infectivity are not currently being 
used on human dura mater, and that there are no validated methods currently available 
that do not decrease the clinical utility of dura mater. Therefore,  1271.220(d) requires 
use of a validated process when one is published subject to the exception noted above and 
below. 
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As new validated processes become available, they will be published in the literature. 
You do not have to validate a published procedure; rather, you could verify that a 
previously validated process has been fully and properly implemented in your 
establishment. We recognize that processing methods could be developed that reduce the 
risk of TSE but that render the HCT/P unsuitable for its intended use. Accordingly, you 
are not required to implement a process if it adversely affects the clinical utility of the 
dura mater ( 1271.220(d)(1)). Alternatively, you could validate an equivalent procedure 
for use in your establishment that is at least as effective as a published procedure, without 
adversely affecting the clinical utility of the dura mater. 
 
To assist you in identifying newly published, validated processes, we intend, pursuant to 
good guidance practices set out in 21 CFR 10.115, to advise you when we have identified 
the existence of a published, validated process that reduces the risk of TSE. 
 
 
XIV.  PROCESS CHANGES ( 1271.225) 
 
Under  1271.225, 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 ( 1271.225).  This provision does not apply to manufacturing 
steps other than processing. Changes to verified processes may require either verification or 
validation. However, under  1271.230(c), when changes to a validated process subject to 
 1271.230(a) occur, you must review and evaluate the process and perform revalidation where 
appropriate (see section XV.F. of this guidance). 
 
For example, a switch from one brand of a solution used in processing to another brand of 
solution would be a process change. In this situation, the establishment could verify that the new 
solution performs as intended in a manner that does not introduce, transmit, or spread 
communicable disease agents. 
 
 
XV.  PROCESS VALIDATION ( 1271.230) 
 
A.  What are General Requirements for Process Validation? 
 
Under  1271.230(a), 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. You must document the validation activities 
and results, including the date and signature of the individual(s) approving the validation 
( 1271.230(a)). 
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B.  What is the Difference Between Validation and Verification? 
 
Validation means confirmation by examination and provision of objective evidence 
that particular requirements can consistently be fulfilled ( 1271.3(kk). 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 
( 1271.3(kk)). Validation is performed before a process is used to manufacture HCT/Ps 
(1271.230(a)). 
 
Verification means confirmation by examination and provision of objective evidence 
that specified requirements have been fulfilled ( 1271.3(ll)). Verification of a process is 
performed after a process has been completed and is performed on all products 
undergoing the process. Examples of validation and verification include the following: 
 
Example 1. For sterilization of processing instruments using a standard cycle accepted 
by industry, verification could be accomplished by monitoring cycle parameters such as 
pressure, time, and temperature in each load, as well as by using biological indicators. 
 
Example 2. Cleaning agents used for processing areas and equipment could be selected 
based on literature searches or Environmental Protection Agency (EPA) registration. 
Verification that the manufacturers instructions are followed with respect to dilution and 
contact time is generally sufficient to meet the CGTP requirements. 
 
Example 3. For processes that you design, validation will generally be required. This 
would entail establishing acceptance criteria for each processing step and determining 
through appropriate testing that these criteria can be consistently met. An adequately 
validated process that remains unchanged will generally need less in-process control and 
testing. 
 
C.  How Do I Perform a Validation Study? 
 
The FDA regulations under Part 1271 do not specify how to perform a validation study. 
The FDA guidance entitled, Guidance for Industry: Validation of Procedures for 
Processing of Human Tissues Intended for Transplantation dated March 2002 (Ref. 12), 
provides information about validation. The recommendations in the FDA guidance 
entitled, Guidance for Industry: Process Validation: General Principles and Practices 
dated January 2011 (Ref. 9), also may be useful to consider. Validation studies 
conducted by your establishment or by experts in the field could be acceptable. For 
example, you could obtain validation data to document the effectiveness of a process to 
prevent contamination in several ways, such as: 
 
  verifying full and proper implementation of a previously validated procedure 
such as a procedure found in a technical manual of another organization; 
  conducting literature searches to demonstrate that the procedures implemented 
are known to be effective in preventing infectious disease contamination (e.g., 
EPA-registered chemical sterilants for laboratory surfaces); or 
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  conducting off-line or on-line challenges with indicator organisms to evaluate 
the capacity of a process to prevent contamination. 
 
Example: You are performing a validation study for your disinfection process (e.g., 
antibiotic soak). Such a study should include steps to address bacteriostasis and 
fungistasis due to residual processing agents that could result in false negative culture 
results. 
 
D.  What Information Should I Collect for Processes that Must be Validated? 
 
You must ensure that you are using effective processes to prevent infectious disease 
contamination and cross-contamination (see  1271.145, 1271.220(a) and 1271.230(a)). 
We encourage you to evaluate your current validation data to ensure that they 
demonstrate that your processes will reliably prevent contamination and cross- 
contamination. In your evaluation, you should consider whether your procedures are 
effective as well as whether your validation is adequate. 
 
For example, you should have information such as: 
 
  whether cleaning agents and procedures used on processing equipment and 
surfaces are effective in removing or inactivating adventitious agents, so that 
HCT/Ps are not cross-contaminated; and 
  whether there have been repeated instances where test results and/or adverse 
reaction reports indicate that the final product is contaminated. 
 
E.  What is Required if I Make a Written Representation That My Processing 
Methods Reduce the Risk of Transmission of Communicable Disease by an 
HCT/P? 
 
Under  1271.230(b), 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. 
 
F.  What Must I Do When I Make Changes to a Validated Process? 
 
Under  1271.230(c), when changes to a validated process subject to  1271.230(a) 
occur, you must review and evaluate the process and perform revalidation where 
appropriate. You must document these activities ( 1271.230(c)). The requirements for 
changes to verified processes, as well as the approval and communication required for 
changes to either verified or validated processes is included in section XIV of this 
guidance. 
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Examples of process changes that would require validation include changing the 
following: 
 
  type of antibiotic used in a processing reagent; 
  concentration of a reagent used for processing; 
  amount of time that an HCT/P is exposed to a reagent; 
  temperature during processing; and 
  lyophilization cycle of a freeze-dryer where the change in cycle could 
reasonably be expected to cause contamination or cross-contamination. 
 
 
XVI.  LABELING CONTROLS ( 1271.250) 
 
A.  What Procedures Must I Establish and Maintain to Control the Labeling of 
My HCT/Ps? 
 
Section 1271.250(a) and (b) requirements are core CGTP requirements 
( 1271.150(b)(7)). Therefore, you must establish and maintain procedures in accordance 
with  1271.180 to control the labeling of HCT/Ps. You must design these procedures to 
ensure proper HCT/P identification and to prevent mix-ups ( 1271.250(a)). Examples of 
procedures that you could use to prevent mix-ups include the following: 
 
  identifying dedicated work areas and controlling separation of activities; 
  enclosing an extra label in the processing record as evidence of the actual 
label used (or for electronic systems you could retain an electronic copy); 
  labeling the HCT/Ps from one donor at a time; and 
  confirming that all extra labels or prelabeled containers issued for HCT/Ps 
obtained from a specific donor have been reconciled and removed from the 
work area. 
 
B.  What Control Procedures Must I Use to Verify Label Accuracy, Legibility, 
and Integrity? 
 
To ensure proper identification of HCT/Ps at every step of manufacturing, your 
procedures must include verification of label accuracy, legibility, and integrity 
( 1271.250(b)). Each establishment has the flexibility to define the methods of control 
for complying with the requirements. 
 
Example: One way to verify identification of donors and HCT/Ps at recovery would be 
to have multiple personnel examine the labels. If a recovery establishment uses hand- 
generated labels, one way to verify the accuracy and legibility is to use indelible ink and 
fixative to ensure label integrity. 
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C.  What Labeling Requirements Apply to My HCT/P? 
 
Under  1271.250(c) your procedures must ensure that each HCT/P is labeled in 
accordance with all applicable labeling requirements, including those in the following 
regulations: 
 
  records accompanying an HCT/P ( 1271.55); 
  HCT/Ps in quarantine ( 1271.60); 
  storage and use of HCT/Ps from a donor determined to be ineligible 
( 1271.65); 
  HCT/Ps from donors excepted from the donor eligibility requirements 
( 1271.90); 
  tracking of HCT/Ps ( 1271.290); and 
  labeling ( 1271.370). 
 
D.  Do the CGTP Regulations Specify When Labels Are to be Placed on HCT/P 
Containers? 
 
The labeling provisions in the CGTP requirements do not indicate the time frame for 
placing labels on HCTP containers, other than to specify how certain products must be 
labeled when they are made available for distribution (see 1271.370).  Note that under 
 1271.250, you must design procedures to ensure proper HCT/P identification and to 
prevent mix-ups. 
 
 
XVII.  STORAGE ( 1271.260) 
 
A.  What Storage Area Activities Must I Control? 
 
Under  1271.260(a), you must control your storage areas and stock rooms to prevent the 
following: 
 
  mix-ups, contamination, and cross-contamination of HCT/Ps, supplies, and 
reagents; and 
  an HCT/P being improperly made available for distribution. 
 
You should identify and design areas used for storage of HCT/Ps to facilitate monitoring 
of temperature and locating in-process HCT/Ps, quarantined HCT/Ps, and HCT/Ps that 
have been made available for distribution. Each storage area should have signs indicating 
the types of supplies, reagents, and HCT/Ps contained in that area, and should be 
organized to prevent mix-ups, cross-contamination, and improper release of HCT/Ps. 
 
Before the completion of the donor-eligibility determination, you must keep an HCT/P in 
quarantine and clearly identify it as in quarantine ( 1271.60(a) and (b)).  The 
quarantined HCT/P must be easily distinguishable from HCT/Ps that are available for 
release and distribution ( 1271.60(b)). Quarantine means the storage or identification of 
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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 
( 1271.3(q)). An example of automated designation is the use of a validated computer 
system to maintain information on bar-code-labeled HCT/Ps held in a freezer. When you 
release the HCT/P, the computer system is activated to ensure identification and retrieval 
of the specific HCT/P for the intended recipient. 
 
B.  How Do I Determine Appropriate Storage Temperatures for My HCT/Ps? 
 
Under  1271.260(b), you must store HCT/Ps at an appropriate temperature. The storage 
temperature should be sufficient to prevent conditions that could increase the risk of 
contamination of each HCT/P stored, considering the types of packaging and 
preservatives used, and the expected duration of storage. There are voluntary standards 
for storage temperatures issued by professional organizations, and you could follow these 
established industry standards where the standards meet the requirements in this section. 
Alternatively, you could establish your own criteria for storage temperature(s) and 
storage period(s) for specific HCT/Ps stored in your facility. See section IX.D. of this 
guidance for further information about monitoring the range of temperatures. 
 
C.  How Do I Determine Whether an Expiration Date Must be Assigned to My 
HCT/Ps? 
 
Where appropriate, you must assign an expiration date to each HCT/P based on the 
following factors ( 1271.260(c)): 
 
  HCT/P type; 
  processing, including the method of preservation; 
  storage conditions; and 
  packaging. 
 
An expiration date based on the factors listed above would be considered appropriate for 
your HCT/P if the absence of a defined expiration date could reasonably be expected to 
result in the product not meeting its specified requirements related to prevention of the 
introduction, transmission, or spread of communicable diseases. We consider it 
appropriate to assign expiration dates for fresh (i.e., non-cryopreserved) HCT/Ps, and for 
HCT/Ps that are thawed or reconstituted prior to administration. If such applicable 
expiration dates have been established by industry or medical practice and meet the 
requirements of this section, you may use those dates for your HCT/Ps, whether fresh or 
preserved. If scientific data do not exist for establishing expiration dates, then an 
expiration date may not be applicable. 
 
Example: Where appropriate, you must assign expiration dates to final products, both 
fresh and cryopreserved, based on the listed factors in  1271.260(c), as needed to ensure 
that they remain free from microbial contamination. It may not be necessary to assign 
expiration dates to HCT/Ps that are cryopreserved, because there is a low risk of 
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contamination as long as they remain immersed in the liquid phase or retained in the 
vapor phase of liquid nitrogen in containers that maintain their integrity and barrier 
properties throughout the storage period. 
 
D.  What Should I Do When Proper Storage Conditions Are Not Met? 
 
You must take and document corrective action whenever proper storage conditions are 
not met ( 1271.260(d)). For example, in response to an alert from your temperature 
monitoring system indicating temperatures outside acceptable limits, you may need to 
transfer your HCT/Ps to an alternative storage area. If the temperature excursion was of 
sufficient duration to increase the risk of contamination, you may need to discard or 
otherwise dispose of the affected products. After taking the appropriate corrective 
action(s), you should document the transfer or other disposition of each affected product. 
 
E.  What Temperature Limits Must I Establish During Manufacturing? 
 
Under  1271.260(e), 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 ( 1271.260(e)). 
You must periodically review recorded temperatures to ensure that temperatures have 
been within acceptable limits ( 1271.260(e)). 
 
Example: If you determine that your HCT/P can be stored at room temperatures, you 
must define the temperature limits (e.g., 20-25 degrees centigrade), and document and 
maintain records of environmental control and monitoring activities ( 1271.260(e) and 
1271.195(a)). These records must be reviewed periodically to ensure that the 
temperatures have been within acceptable limits ( 1271.260(e)). 
 
F.  What Procedures Related to Storage Must I Establish and Maintain? 
 
Section 1271.260(a) through (d) requirements are core CGTP requirements 
( 1271.150(b)(8)). Therefore, you must establish and maintain procedures in accordance 
with  1271.180. 
 
 
XVIII. RECEIPT, PREDISTRIBUTION SHIPMENT, AND DISTRIBUTION OF AN 
HCT/P ( 1271.265) 
 
A.  What Should I Do Before Accepting an HCT/P From Another 
Establishment? 
 
Under  1271.265(a), 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 
( 1271.265(a)). 
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B.  What Are Ways That I Can Evaluate an Incoming HCT/P for 
Microorganisms and Inspect for Damage and Contamination? 
 
When you receive an HCT/P, you should visually inspect the shipping container, 
packaging, HCT/P container, and HCT/P for damage and contamination. If there are 
indications that contamination or cross-contamination of the HCT/P could have occurred, 
you should quarantine the HCT/P until your investigation is complete. 
 
Another method used to evaluate an HCT/P for contamination is to culture the HCT/P 
prior to processing. This culture is known as the pre-processing culture (sometimes 
referred to as the pre-disinfection culture). Recovery establishments may perform the 
culture and send the results to the processor. Alternatively, using pre-established criteria, 
the processor may perform the culture and based upon the results determine whether to 
reject or accept the HCT/P for processing. For instance, some processors may irradiate 
the HCT/P to reduce the bioburden prior to additional processing, depending upon the 
amount and/or type of microorganisms detected. 
 
It may not be possible to culture some HCT/Ps prior to processing. For instance, corneas 
are recovered and then placed immediately into transport media that contains antibiotics. 
While corneas recovered in situ are not processed, they are received at the eye bank 
already packaged in a container with transport media. We recommend that a 
corneoscleral rim culture should be taken at the time of recovery. If the container in 
which the cornea is placed after recovery is not fully intact when received by the eye 
bank, one should assume the possibility of contamination and presence of 
microorganisms. For storage/transport solutions containing a pH indicator, a color 
change could indicate contamination. 
 
C.  What is Predistribution Shipment? 
 
Predistribution shipment is the conveyance or shipment of an HCT/P within your 
establishment or between establishments before it has met its release criteria (i.e., it is not 
available for distribution). The sender must determine and document whether the HCT/P 
has met pre-established criteria designed to prevent communicable disease transmission 
before shipping it. The HCT/P must be kept in quarantine during pre-distribution 
shipment and upon receipt (see  1271.265(a) and (b)). 
 
Example 1: An HCT/P is being shipped from the recovery establishment to the 
processing establishment. The HCT/P should be transported in a shipping container that 
is capable of maintaining the desired temperature during transport and that is capable of 
withstanding physical stress. 
 
Example 2: Predistribution shipment can also occur within one establishment (e.g., 
transported between buildings or transported between floors in the same building before 
the HCT/P is available for distribution). Transferring HCT/Ps from one room to the next 
during processing (between steps) is not considered predistribution shipping. 
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D.  When is an HCT/P Available for Distribution? 
 
Available for distribution means that the HCT/P has been determined to meet all 
release criteria ( 1271.3(z)). 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 ( 1271.3(bb)). 
If an entity does not take physical possession of an HCT/P, the entity is not considered a 
distributor ( 1271.3(bb)). 
 
For example, there are brokers who facilitate HCT/P distribution by identifying potential 
clients/consignees (whether within the United States or for export) in need of particular 
HCT/Ps. If these brokers only match up clients with HCT/P establishments and never 
take physical possession of the HCT/Ps, they would not be considered to be distributors. 
 
Note that these requirements also do not apply with respect to carriers, such as Federal 
Express, United Parcel Service, or the United States Postal Service, who are exempt from 
the regulations in this part as noted in  1271.15(c). 
 
E.  What Must I Do Before Making an HCT/P Available for Distribution? 
 
Before making an HCT/P available for distribution, you must review manufacturing 
records (such as records from the donor eligibility determination, recovery, processing, 
and storage) 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 
( 1271.265(c)(1)). 
 
You must not make available for distribution an HCT/P that: 
 
  is in quarantine; 
  is contaminated (note that skin cultures taken post-processing may be positive 
for non-pathogenic normal flora but this is not considered contamination); 
  is from a donor who has been determined to be ineligible or a donor with an 
incomplete donor eligibility determination (except as provided in  1271.60, 
1271.65, and 1271.90); or 
  otherwise does not meet release criteria designed to prevent communicable 
disease transmission. ( 1271.265(c)(2)). 
 
If the HCT/P establishment maintains records in more than one location, faxing or 
emailing records for review prior to release for distribution is acceptable provided that 
the records can be adequately evaluated (e.g., legible and accurate). 
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F.  Who Must Determine That an HCT/P is Available for Distribution? 
 
A responsible person must make this determination and document and date the 
determination that an HCT/P is available for distribution ( 1271.265(c)(1)). A 
responsible person means a person who is authorized to perform designated functions for 
which he or she is trained and qualified ( 1271.3(t)). 
 
G.  May I Release an HCT/P if it Has Been Manufactured Under a Departure 
From a Procedure? 
 
If you make a departure from a procedure (SOP deviation) that is relevant to preventing 
risks of communicable disease transmission, you must not make an HCT/P manufactured 
under the departure available for distribution, unless a responsible person has determined 
that the departure does not increase the risk of communicable disease through the use of 
the HCT/P ( 1271.265(c)(3)). You must record and justify any departure from a 
procedure at the time of its occurrence ( 1271.265(c)(3)). 
 
Example 1: You arrive at a recovery site to recover HCT/Ps from a deceased donor and 
you discover that the cleaning solution that you routinely use to disinfect the work 
surface is not available. You clean the surface with an alternative cleaning solution and 
proceed to recover HCT/Ps. The HCT/Ps are sent to a processing establishment. The 
HCT/Ps must not be made available for distribution until a responsible person determines 
that use of the alternate cleaning solution does not increase the risk of HCT/P 
contamination ( 1271.265(c)(3)). 
 
Example 2: You are processing a hematopoietic stem cell product in the LFH. While 
engaged in aseptic processes you realize that the reagent you placed in the hood is a new 
in-house reagent that meets specifications designed to prevent transmission of 
communicable disease, but your establishments SOP has not yet been updated to reflect 
the acceptance of the new reagent. The reagent specified in the SOP is not immediately 
available in your laboratory. You complete the aseptic processing using the new reagent 
and then immediately document the departure from procedure. The cell product must not 
be made available for distribution until a responsible person determines that use of the 
new reagent does not increase the risk of contamination of the product 
( 1271.265(c)(3)). 
 
H.  Does a Distributor Need to Make an Assessment that the HCT/P is Available 
for Distribution? 
 
The establishment that determines that the HCT/P is available for distribution must 
comply with  1271.265(c). This could be the distributor or the processing 
establishment, depending upon the arrangement between the two. 
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I.  Am I Required to Validate or Verify Packaging and Shipment of HCT/Ps? 
 
Process validation or verification only applies to processing ( 1271.3(ff) and 
1271.230(a)). Since packaging and shipping are not part of processing, they are not 
required to be validated or verified. The packaging and shipping containers must be 
designed and constructed to protect the HCT/P from contamination ( 1271.265(d)). 
 
J.  Am I Required to Determine the Appropriate Shipping Conditions? 
 
For each type of HCT/P, you must establish appropriate shipping conditions to be 
maintained during transit ( 1271.265(d)). You could use industry standards, if available, 
or establish for yourself appropriate temperature and time limits during shipping. It is 
also important to ensure that appropriate conditions are maintained throughout 
distribution. If you have a contract, agreement or other arrangement with distributors, 
sub-distributors and/or sales agents who distribute, you should ensure that appropriate 
conditions will be maintained before entering into such contracts, agreements or other 
arrangements. 
 
K.  What Procedures and Documentation Must I Have for Receipt, 
Predistribution Shipment, and Distribution of an HCT/P? 
 
Section 1271.265(a) through (d) requirements are core CGTP requirements 
( 1271.150(b)(9)). Therefore, you must establish and maintain procedures in accordance 
with  1271.180. Under  1271.265(e), you must establish and maintain procedures, 
including release criteria, for receipt, predistribution shipment, availability for 
distribution, and packaging and shipping. You must document these activities 
( 1271.265(e)). Documentation must include the following: 
 
  identification of the HCT/P; 
  identification of the sender (establishment that supplied the HCT/P); 
  activities that you performed on the HCT/P (e.g., inspection, acceptance or 
rejection of the HCT/P) and the results of each activity; 
  date(s) of activity; 
  quantity of HCT/P subject to the activity (e.g., received or distributed); and 
  disposition of the HCT/P (e.g., identity of the consignee to whom the HCT/P 
was sent) ( 1271.265(e)(1) through (5)). 
 
For example, you could accomplish this with a checklist or a packing list. 
 
L.  Is an Establishment Such as a Hospital That Only Receives and Stores 
HCTP/s Required to Register Under  1271.1(b)? 
 
In accordance with  1271.15(d), a hospital that only receives or stores HCT/Ps solely for 
implantation, transplantation, infusion, or transfer within its facility, but does not recover, 
screen, test, process, label, package, or distribute HCT/Ps, is not required to register. 
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However, if a hospital sends the HCT/P to other establishments (e.g., other hospitals or 
ambulatory sites), the hospital is functioning as a distributor and is required under 
 1271.1(b) to register and list its HCT/Ps. 
 
M.  Am I Permitted to Place Returned HCT/Ps Back Into Inventory? 
 
Under  1271.265(f), 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. If 
return is not permitted, this should be made clear to the consignee. If return is permitted, 
you should specify the conditions under which the return could be returned to inventory. 
 
 
XIX.  RECORDS ( 1271.270) 
 
A.  What are the General Requirements for Records? 
 
Under  1271.270(a), you must maintain records concurrently with the performance of 
each step required in Part 1271, Subparts C and D. All required records must be 
accurate, indelible, and legible. 
 
To help ensure the accuracy of records retained, we recommend that establishments that 
make an HCT/P available for distribution obtain records directly from the creator of such 
documents whenever possible (e.g., serology/microbiology results should be obtained 
directly from the testing laboratory; death certificates, if needed to make an adequate 
donor eligibility determination, should be obtained directly from the state health official). 
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 ( 1271.270(a)). 
For specific requirements for retention of donor eligibility records, see  1271.55(d). 
 
B.  What Kind of Records Management System Must I Have? 
 
Under  1271.270(b), you must establish and maintain a records management system 
relating to core CGTP requirements. Under this system, you must maintain records 
pertaining to a particular HCT/P 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 follow-up evaluation or investigation ( 1271.270(b)). You 
must also maintain and organize records pertinent to the manufacture of the HCT/P (e.g., 
labeling and packaging procedures, and equipment logs) under the records management 
system ( 1271.270(b)). If you maintain records in more than one location, you must 
design the records management system to ensure prompt identification, location, and 
retrieval of all records ( 1271.270(b)). 
 
The regulations do not specify the details of a records management system. You should 
organize your records in a useful manner in accordance with the requirements in this 
section. 
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Example: A recovery establishment under contract with a processor sends HCT/Ps to the 
processor. The recovery establishment should send all relevant records, including donor 
records and records relating to recovery site suitability as described in section XII.B., to 
the processor. The recovery establishment must maintain copies of all transferred records 
and organize them in its records management system. 
 
C.  What Are Acceptable Methods of Record Retention? 
 
Under  1271.270(c), you may maintain records 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 ( 1271.270(c)). You must back up records stored 
in electronic systems ( 1271.270(c)). 
 
Example: You are a processor that receives paper records of the donors medical history 
from the recovery establishment. You review the medical history as part of the donor 
eligibility determination. At a later time, you scan the paper records and save them as a 
.pdf file on a computer that is backed up. The electronic records are true copies of the 
paper records. Therefore, you may destroy the paper records. However, if instead of 
scanning, you were to re-type (transfer) the information into the computer, you would be 
creating a new record, not making a true copy. Errors may have been made while re- 
typing, either intentionally or unintentionally. So in this scenario, you would be required 
to keep the original paper (hardcopy) records as proof of concurrent recordkeeping 
( 1271.270(a)). 
 
D.  For How Long Must I Retain my HCT/P Manufacturing Records? 
 
Under  1271.270(d), you must retain all records for 10 years after their creation, unless 
stated otherwise in Part 1271. 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 ( 1271.270(d)). You must 
retain records for archived specimens of dura mater for 10 years after the appropriate 
disposition of the specimens ( 1271.270(d)). 
 
Laboratories that perform communicable disease testing of donor specimens and/or 
microbiological testing of HCT/Ps would not know the date of administration, 
distribution, disposition, or expiration. These laboratories would be required to keep 
donor testing information for 10 years after the creation of the record ( 1271.270(d)) 
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Example: A cord blood establishment goes out of business, and transfers the remaining 
products in inventory to one or more different cord blood establishments. All of the 
original manufacturing records or complete copies for these products were transferred to 
the establishment(s) receiving the cord blood. The receiving establishment(s) will be 
responsible for maintaining those records in such a way as to facilitate review of an 
HCT/Ps history before making it available for distribution and, if necessary, subsequent 
to the HCT/Ps release as part of a follow up evaluation or investigation ( 1271.270(b)). 
The receiving establishment(s) must maintain the manufacturing records for at least 10 
years after the date the HCT/P is administered ( 1271.270(d)). 
 
E.  What Records of Contracts and Agreements Must I Maintain? 
 
Under  1271.270(e), you must maintain the name and address and a list of the 
responsibilities of any establishment that performs a manufacturing step for you (see 
 1271.150(c)(1)). You must have this information available during an inspection 
conducted under  1271.400 ( 1271.270(e)). We recommend that contracts, agreements 
or other arrangements describe the responsibilities of all parties. For instance, a contract, 
agreement or other arrangement with an individual or establishment who obtains the 
donors hospital records should describe the information that you want that individual or 
establishment to obtain. 
 
For example, when donor eligibility is determined following a review of records obtained 
by another establishment, the contract, agreement or other arrangement might specifically 
identify what records will be obtained, in what format they will be provided, 
responsibilities for record retention and access, and if the reviewing firm will convey 
donor eligibility conclusions back to the firm that collected the information. 
 
 
XX.  TRACKING ( 1271.290) 
 
Under  1271.290(a), 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. You must perform tracking in accordance 
with Part 1271, to facilitate the investigation of an actual or suspected transmission of a 
communicable disease and to take appropriate and timely corrective action ( 1271.290(a)). If 
you do not handle the HCT/P (e.g., you are the testing laboratory that receives a blood specimen, 
but you do not actually handle the HCT/P), you do not have to participate in the tracking 
requirements. 
 
A.  How Extensive a Tracking System Must I Establish and Maintain? 
 
You must have a tracking system in place that enables the HCT/P to be tracked from the 
donor to the receiving facility (consignee) or final disposition and back to the donor 
( 1271.290(b)(1)). 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 
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establishment responsible for other steps in the manufacture of the same HCT/P, 
provided that the tracking system complies with all  1271.290 requirements 
( 1271.290(b)(2)). You should verify that the tracking system is effective, especially if 
you participate in a tracking system maintained by another establishment. Each 
establishment has the flexibility to define the tracking system and ensure that the 
establishment meets the requirements for tracking. 
 
B.  Must Each HCT/P Have a Distinct Identification Code? 
 
Under  1271.290(c), each HCT/P that you manufacture must be assigned and labeled 
with a distinct identification code that relates the HCT/P to the donor and to all records 
pertaining to the HCT/P. The code must be created specifically for tracking purposes and 
may not include an individuals name, social security number or medical record number 
(with some exceptions as noted below) (See  1271.290(c)). You may adopt the distinct 
identification code assigned by another establishment engaged in manufacturing, or 
assign a new code, but you should verify and/or validate that your tracking system is 
effective. The distinct identification code must be able to be related to the donor 
( 1271.290(c)) but does not necessarily have to be on all records concerning the donor or 
on the package insert. However, the distinct identification code must be affixed to the 
HCT/P container ( 1271.370(b)(1)). 
 
As described in  1271.290(c), the HCT/P establishment cannot assign an individuals 
name, social security number, or hospital medical record number as the HCT/P distinct 
identification code. However, these are acceptable for use in the case of autologous, 
directed reproductive, or first-degree or second-degree blood relative donations 
( 1271.55(a)(1)). 
 
C.  How Do I Ensure Tracking of HCT/Ps Distributed From My Establishment 
to Consignees or for Final Disposition? 
 
Under  1271.290(d) 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( 1271.290(d)). In 
addition, 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 ( 1271.290(e)). This information must permit the 
prompt identification of the consignee of the HCT/P, if any ( 1271.290(e)). 
 
Under  1271.290(f), 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  1271.290 and of the 
tracking system that you have established and are maintaining to comply with these 
requirements. 
 
As part of the tracking system, you should inform the consignee that the consignee 
should record a distinct identification code in a record and in the patients file, and that 
the consignee should complete and return HCT/P disposition information according to 
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the established instructions. You could also supply self-addressed envelopes, or an email 
or web address to return the disposition information for your tracking system. Reminders 
could be sent to hospitals or other consignees (e.g., surgical centers, dental offices) when 
disposition information is not received. You might also enhance consignee feedback by 
providing your consignee with labels that identify each product and the establishment that 
provided it, and tracking logs for the hospitals to use to control inventory. 
 
D.  Are There Specific Requirements for Dura Mater Donors? 
 
Under  1271.290(g), 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 TSE, and to enable appropriate 
disposition of any affected non-administered dura mater tissue, if necessary. Examples of 
appropriate specimens are serum or lymph nodes. We also recommend that you archive 
frozen and fixed samples of both donor brain and dura mater HCT/Ps. The donor brain 
samples should include at least 5 grams of the frontotemporal region.  We recommend 
that you retain these specimens for 10 years based on the current scientific knowledge 
regarding the development of screening tests and expectation that, as the science evolves, 
screening tests could become available. You must retain records for archived specimens 
of dura mater for 10 years after the appropriate disposition of the specimens ( 
1271.270(d)). 
 
 
XXI.  COMPLAINT FILE ( 1271.320) 
 
Under  1271.320(a), you must establish and maintain procedures for the review, evaluation, and 
documentation of complaints relating to core CGTP requirements, and the investigation of 
complaints as appropriate. A complaint ( 1271.3(aa)) is any written, oral, or electronic 
communication about a distributed HCT/P that alleges the following: 
 
  that the HCT/P has transmitted or may have transmitted a communicable disease to 
the recipient of the HCT/P; or 
  any other problem with an HCT/P relating to the potential for transmission of 
communicable disease, such as the failure to comply with CGTP requirements. 
 
A.  What Information About Each Complaint Must I Have in My Complaint 
File? 
 
Under  1271.320(b), 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 ( 1271.320(b)). You 
must make the complaint file available for review and copying upon request from FDA 
( 1271.320(b)). We may make requests for review of complaint files by telephone, fax, 
mail, or in person. When copying complaint files, we are required to maintain the 
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confidentiality of the records/files and protect the information from inappropriate release 
under the Standards for Privacy of Individually Identifiable Health Information (67 FR 
53181, August 14, 2002) and other applicable laws and regulations. 
 
B.  How Should I Review and Evaluate Complaints? 
 
Under  1271.320(c), 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 other applicable 
regulation is required. An event that must be reported to FDA as described in  1271.350 
(e.g., an adverse reaction related to communicable disease transmission), must be 
reviewed, evaluated, and investigated as soon as practical. 
 
For complaints relating to core CGTP requirements that are not required to be reported, 
you must still perform a review and evaluation to determine whether an investigation is 
necessary ( 1271.320(c)). An investigation may include referring a copy of the 
complaint to another establishment that performed manufacturing steps pertinent to the 
complaint ( 1271.320(c)). 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 ( 1271.320(c)). 
 
 
XXII.  REPORTING ( 1271.350) 
 
Under  1271.330, the  1271.350 reporting requirements apply only to nonreproductive HCT/Ps 
described in  1271.10 regulated solely under section 361 of the PHS Act.  HCT/Ps that are 
drugs or devices regulated under the FD&C Act, or are biological products regulated under 
section 351 of the PHS Act, are not subject to these reporting requirements. 
 
A.  What Are the General Requirements for Adverse Reaction Reports? 
 
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 ( 1271.3(y)). We 
recognize that there may be situations in which there are multiple possible causes of a 
patients problem. Nevertheless, if one of the reasonable possibilities is that the HCT/P 
caused the problem, then this would meet the definition of adverse reaction. This 
would include situations in which the relationship between the response and the HCT/P is 
unlikely but nevertheless possible. 
 
Under  1271.350(a)(1), you must investigate any adverse reaction involving a 
communicable disease related to an HCT/P that you made available for distribution. In 
addition, under  1271.350(a)(1) you must report to FDA an adverse reaction involving a 
communicable disease if it: 
 
  is fatal; 
  is life-threatening; 
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  results in permanent impairment of a body function or permanent damage to 
body structure; or 
  necessitates medical or surgical intervention, including hospitalization. 
 
If the adverse reaction does not involve a communicable disease transmission (e.g., 
primary graft failure after corneal transplantation, hemolysis due to an ABO- 
incompatibility in a patient who has received hematopoietic stem/progenitor cells), you 
do not have to report to FDA such an adverse reaction. 
 
Example 1: A patient has surgery on his knee following an injury, and receives a patellar 
tendon.  Several days after the surgery, the patient develops severe pain in the knee.  He 
is taken back to the operating room, where his knee is examined. Purulent fluid is 
removed. This fluid is cultured and grows Methicillin resistant Staphylococcus aureus 
(MRSA). The surgeon contacts the HCT/P establishment. The medical director reviews 
the donors records and the manufacturing records for the tendon. The pre-processing 
cultures were positive for MRSA, but the post-processing cultures were negative. The 
validation studies for the antibiotic soaking process are reviewed and seem to be in order. 
You must report this adverse reaction, even though the post-processing cultures were 
negative, because there is a reasonable possibility that the HCT/P caused the response, 
the adverse reaction involves a communicable disease, and it necessitated medical 
intervention. 
 
Example 2: A patient develops endophthalmitis after receiving a cornea allograft. A 
posterior chamber culture grows Staphylococcus epidermidis. Although the eye bank did 
not culture the cornea prior to release, the surgeon performed a pre-implant culture, 
which was negative. The surgeon ordered additional antibiotics to treat the 
endophthalmitis. You must report this adverse reaction, even though the pre-implant 
culture was negative, because there is a reasonable possibility that the cornea caused this 
response, the adverse reaction involves a communicable disease, and it necessitated 
medical intervention. 
 
Example 3:  A patient spikes a fever and develops shaking chills 45 minutes after 
infusion of autologous peripheral blood stem cells. The patient had already received 
antibiotics for two days prior to the infusion for febrile neutropenia following high dose 
chemotherapy, but had no fever at the start of the infusion. The treating physician 
determines that the febrile reaction is not related to the HCT/P and the patients antibiotic 
regimen is not modified. You would not be required to report this adverse reaction 
because no additional intervention was necessary and there is not a reasonable possibility 
that the HCT/P caused the response. 
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B.  What is Considered a Medical or Surgical Intervention That I Must Report 
to FDA? 
 
For purposes of  1271.350(a)(1)(iv), a medical or surgical intervention is an action, 
outside the bounds of the medical treatment normally given after administration of an 
HCT/P, which is intended to treat known or suspected transmission of communicable 
disease or infection affecting the patient. Following a thorough review, the establishment 
that made the HCT/P available for distribution should decide the following: 
 
  if the adverse reaction involves a communicable disease; and 
  whether or not there is a reasonable possibility that the adverse reaction is 
related to the HCT/P. 
 
Example 1. Medical intervention would include prescribing, increasing the dose of, or 
changing an antibiotic outside the bounds of normal post-operative treatment for 
treatment of a known or suspected infection. 
 
Example 2. Medical intervention would include re-hospitalizing a patient who was 
discharged following surgery for treatment of a known or suspected infection, or its 
consequences. 
 
Example 3. Surgical intervention would include returning a patient to the operating room 
or performing an incision and drainage procedure in the clinic for treatment of a known 
or suspected infection, or its consequences. 
 
C.  How Do I Report Adverse Reactions to FDA? 
 
You must submit to FDA each report of an adverse reaction on a Form FDA 3500A 
within 15 calendar days of initial receipt of the information ( 1271.350(a)(2)). You can 
find additional information about how to report adverse reactions in the Guidance for 
Industry: MedWatch Form FDA 3500A: Mandatory Reporting of Adverse Reactions 
Related to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) 
(Ref. 2). This guidance provides supplemental instructions for reporting using the 
MedWatch Form FDA 3500A. You can find additional information on reporting on 
FDAs tissue webpage at 
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/ucm152 
576.htm. 
 
D.  What Kind of Information Should I Review When Investigating Adverse 
Reactions? 
 
We recommend that you review the following information while investigating reports of 
adverse reactions: 
 
  pre- and post-processing culture results; 
  donor screening records; 
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Contains Nonbinding Recommendations 
  donor testing results; 
  donor eligibility determination; 
  donor identification code; 
  lot number; 
  receipt of complaints involving recipients of other HCT/Ps from the same 
donor; and 
  the occurrence of any processing deviations from your established SOPs. 
 
Examples of additional information you might review if obtainable: 
 
  results of pre-implant cultures (collected by the implanting facility just prior 
to transplantation); 
  date of implantation/explanation; 
  symptoms of infection in the recipient and dates of onset; 
  recipients serologic or culture results; 
  medical and surgical interventions required; 
  pathology reports; 
  recipients risk factors if available; 
  physicians impression about the cause of the infection; and 
  recipients clinical records. 
 
E.  When Do I Submit a Followup Report to FDA? 
 
Under  1271.350(a)(3), you must submit to FDA followup reports within 15 calendar 
days of the receipt of new information or as requested by FDA. If additional information 
is not obtainable, you may be required to submit a followup report describing briefly the 
steps taken to seek additional information and the reasons why it could not be obtained. 
 
F.  What Procedures Did FDA Develop to Handle Adverse Reaction Reports for 
HCT/Ps? 
 
CBER formed a Tissue Safety Team to review and monitor adverse reaction reports and 
to investigate them as necessary. We developed SOPPs to ensure that the 
responsibilities for addressing reported adverse reactions associated with HCT/Ps are 
clearly established. The SOPP 8508, Procedures for Handling Adverse Reaction 
Reports Related to 361 Human Cells, Tissues, and Cellular and Tissue-Based Products 
(HCT/Ps) (Ref. 13), describes the procedures that CBER routinely follows when 
receiving and investigating adverse reaction reports associated with HCT/Ps. 
 
G.  How Do I Report an HCT/P Deviation to FDA? 
 
Under  1271.350(b)(3), you must report each HCT/P deviation that relates to a core 
CGTP requirement on Form FDA 3486, available at 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM061463.p 
df, within 45 days of the discovery of the event. The form may be submitted either 
electronically at 
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http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/Biologi 
calProductDeviations/ucm134534.htm or by mail to the Director, Office of Compliance 
and Biologics Quality, Center for Biologics Evaluation and Research (HFM-600), 1401 
Rockville Pike, suite 200N, Rockville, MD 20852-1448. 
 
H.  What Are the General Requirements for HCT/P Deviation Reporting? 
 
Under  1271.3(dd), an HCT/P deviation means an event: 
 
  that represents a deviation from applicable regulations in Part 1271 or from 
applicable standards or established specifications that relate to the prevention 
of communicable disease transmission or HCT/P contamination 
( 1271.3(dd)(1)); or 
  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 ( 1271.3(dd)(2)). 
 
Under  1271.350(b)(1), you must investigate all HCT/P deviations related to a 
distributed HCT/P for which you performed a manufacturing step. 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 ( 1271.350(b)(2)). Under 
 1271.350(b)(2), 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). 
 
 
XXIII. LABELING ( 1271.370) 
 
Under  1271.330, the labeling requirements in  1271.370 apply only for non-reproductive 
HCT/Ps described in  1271.10 that are regulated solely under section 361 of the PHS Act. 
HCT/Ps that are drugs or devices regulated under the FD&C Act, or are biological products 
regulated under section 351 of the PHS Act, are not subject to these labeling requirements. 
 
A.  What Information Must Appear on the HCT/P Label? 
 
Under  1271.370(a), you must label each HCT/P made available for distribution clearly 
and accurately. Note that a label can include the affixed container label or an attached 
tie-tag. You must place the following information on the HCT/P label ( 1271.370(b)): 
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  distinct identification code affixed to the HCT/P container, and assigned in 
accordance with  1271.290(c) ( 1271.370(b)(1)); 
  description of the type of HCT/P ( 1271.370(b)(2)); 
  expiration date, if any ( 1271.370(b)(3)); and 
  warnings required under  1271.60(d)(2), 1271.65(b)(2), or 1271.90(b), if 
applicable and physically possible. If it is not physically possible to include 
these warnings on the label, the warnings must accompany the HCT/P 
( 1271.370(b)(4)). . 
 
B.  Is the Manufacturer Expected to Place the Distinct Identification Code on 
Information That Accompanies Each Distributed HCT/P? 
 
Under  1271.370(b)(1), the distinct identification code must be affixed to the HCT/P 
container and assigned in accordance with  1271.55(a)(1) and 1271.290(c). There is 
no requirement that the distinct identification code appear on other information 
accompanying the HCT/P, such as the instructions for use described in  1271.370(c). 
Additionally, there is no requirement to place the distinct identification code on the 
summary of records described in  1271.55(b). However, your labeling procedures 
should be designed to ensure that consignees can readily link the product to all required 
labeling and accompanying records, such as instructions for use. 
 
C.  What Additional Information Must Appear on the HCT/P Label or 
Accompany the HCT/P? 
 
Under  1271.370(c), the following information must either appear on the HCT/P label or 
accompany the HCT/P: 
 
  name and address of the establishment that determines that the HCT/P meets 
release criteria and makes the HCT/P available for distribution 
( 1271.370(c)(1); 
  storage temperature ( 1271.370(c)(2)); 
  other warnings, where appropriate ( 1271.370(c)(3)); and 
  instructions for use when related to the prevention of the introduction, 
transmission, or spread of communicable diseases ( 1271.370(c)(4)). 
 
D.  How Can I Maintain Privacy with Regard to the Warning Statements? 
 
If it is physically possible to include some or all of the warning statements on the HCT/P 
container label, but there are concerns about displaying private information (e.g., to 
family members or other visitors present in the patients room while an HCT/P is being 
administered), it is acceptable to place the warning statements on the HCT/P container 
label or an attached tie-tag in a manner that limits visibility to visitors but allows clear 
display of the information to the healthcare providers administering the HCT/P. 
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E.  Must the Name and Address of the Processing Establishment, if Different 
From the Establishment That Determines That the HCT/P Meets Release 
Criteria and Makes it Available for Distribution, be Included on the Label or 
Other Accompanying Information Provided to the Consignee? 
 
You are not required to include the names of all establishments that performed 
manufacturing steps in the labeling. Under  1271.370(c)(1), only the name and address 
of the establishment that determines that the HCT/P meets release criteria and makes the 
HCT/P available for distribution must appear on the HCT/P label or accompany the 
HCT/P. Note that the name and address of the establishment that made the donor- 
eligibility determination must appear in the summary of records that accompanies the 
HCT/P ( 1271.55(b)). 
 
However, if the establishment that makes the donor-eligibility determination is not the 
same establishment that makes the HCT/P available for distribution, the labeling or 
accompanying information should contain the name and address of both establishments 
and specify which establishment performed which function. 
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XXIV. REFERENCES 
 
1. Food and Drug Administration. Guidance for Industry: Eligibility Determination for Donors 
of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), August 2007. 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/G 
uidances/Tissue/ucm073964.htm 
2. Food and Drug Administration. Guidance for Industry: MedWatch Form FDA 3500A: 
Mandatory Reporting of Adverse Reactions Related to Human Cells, Tissues, and Cellular 
and Tissue-Based Products (HCT/Ps), November 2005. 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/G 
uidances/Tissue/ucm074000.htm 
3. Food and Drug Administration. SOPP 9151: Procedures for Handling Requests for 
Exemptions and Alternative Procedures for Human Cells, Tissues, and Cellular and Tissue- 
Based Products ( HCT/Ps) Under 21 CFR Section 1271.155, June, 13, 2006, 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Pr 
oceduresSOPPs/ucm063375.htm 
4. Food and Drug Administration. CPG Sec. 130.300 FDA Access to Results of Quality 
Assurance Program Audits and Inspections, June 2, 2007, 
http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm073 
841.htm 
5. Food and Drug Administration. General Principles of Software Validation; Final Guidance 
for Industry and FDA Staff, January 11, 2002. 
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDo 
cuments/UCM085371.pdf 
6. Food and Drug Administration. Guidance for Industry: Sterile Drug Products Produced by 
Aseptic Processing  Current Good Manufacturing Practice, September 2004, 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance 
s/UCM070342.pdf 
7. Chapter <1116> Microbiological Evaluation of Clean Rooms and Other Controlled 
Environments. US Pharmacopoeia 30, United States Pharmacopoeia Convention, Inc., 
Rockville, MD: 2007. 
8. Food and Drug Administration. Class II Special Controls Guidance Document: Human Dura 
Mater, Guidance for Industry and FDA Staff, December 18, 2003, 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/uc 
m072657.htm 
9. Food and Drug Administration. Guidance for Industry: Process Validation: General 
Principles and Practices, January 2011, Revision 1 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance 
s/UCM070336.pdf 
10.  Food and Drug Administration. Quick Summary: Transmissible Spongiform 
Encephalopathies Advisory Committee, July 17-18, 2003, 
http://www.fda.gov/ohrms/dockets/ac/03/minutes/3969M.pdf 
11.  CDC. Update: Allograft-Associated Bacterial Infections---United States, 2002 MMWR, 
2002:51:207-210. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5110a2.htm 
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12.  Food and Drug Administration. Guidance for Industry: Validation of Procedures for 
Processing of Human Tissue Intended for Transplantation, March 2002, 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/G 
uidances/Tissue/ucm073429.htm 
13.  Food and Drug Administration. SOPP 8508: Procedures for Handling Adverse Reaction 
Reports Related to 361 Human Cells, Tissues, and Cellular and Tissue-Based Products 
(HCT/Ps), Version #2 March, 26, 2008 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Pr 
oceduresSOPPs/ucm073048.htm 
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