Guidance for Industry
 
 
Compliance with 21 CFR Part 
1271.150(c)(1)  Manufacturing 
Arrangements
 
 
 
 
 
 
 
 
This guidance is for immediate implementation. 
 
 
 
FDA is issuing this guidance for immediate implementation in accordance with 21 CFR 
10.115(g)(4)(i).  Submit written comments on this guidance at anytime to the Division of 
Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852.  Submit electronic comments to http://www.fda.gov/dockets/ecomments.  
You should identify all comments with the title of this guidance.   
 
Additional copies of this guidance are available from the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at 
http://www.fda.gov/cber/guidelines.htm. 
 
For questions on the content of this guidance, contact the Office of Compliance and Biologics 
Quality, at (301) 827-6190. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
September 2006  Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................2 
III.  DISCUSSION....................................................................................................................2 
A.  Am I Responsible for Ensuring that Establishments that I Have 
Manufacturing Arrangements with are in Compliance with CGTP 
Requirements?.......................................................................................................2 
B.  What Additional Information would be Helpful to Me in Understanding My 
Responsibilities for Manufacturing Arrangements?.........................................2 
IV.  SUMMARY.......................................................................................................................3 
V.  REFERENCES..................................................................................................................3 
i  Contains Nonbinding Recommendations 
 
Guidance for Industry 
 
Compliance with 21 CFR Part 1271.150(c)(1)  Manufacturing 
Arrangements 
 
 
 
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 emphasize to you, establishments that manufacture human 
cells, tissues, and cellular and tissue-based products (HCT/Ps), your responsibility to comply 
with Title 21 Code of Federal Regulations 1271.150(c)(1) (21 CFR 1271.150(c)(1)), if you enter 
into a contract, agreement, or other arrangement with another establishment to perform for you 
any step in manufacture.  (Ref. 1).  If you engage another establishment to perform for you any 
step in manufacture, that establishment must comply with requirements applicable to that 
manufacturing step (21 CFR 1271.150(c)(1)(i) and (ii)).  The intent of this guidance is to 
highlight your responsibilities in ensuring that establishments that engage in any step in 
manufacture for you are in compliance with the current good tissue practice (CGTP) 
requirements of the HCT/P regulations in 21 CFR Part 1271.   
 
FDA evaluates compliance with CGTP and, where needed, takes compliance actions to stop 
recovery or other practices which do not meet applicable requirements.  We also evaluate during 
an FDA investigation an establishments actions to ensure that contracting establishments 
comply with applicable CGTP requirements if they perform one or more manufacturing steps for 
the establishment.  Your activities to ensure that contracting establishments comply with 
applicable CGTP requirements can help identify and prevent problems such as those observed 
during recent FDA investigations.  Your actions help prevent undue risks to product quality and 
patient safety.  
 
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. 
 
 
1  Contains Nonbinding Recommendations 
 
 
II.  BACKGROUND 
 
FDAs recently implemented HCT/P regulations addressing CGTP, including those in 21 CFR 
1271.150(c)(1), are effective for HCT/Ps recovered on or after May 25, 2005.  Ongoing FDA 
investigations of some recovery establishments under contract, agreement, or other arrangement 
with processing establishments have identified significant violations of CGTP requirements, 
which may put some tissue recipients at potentially increased risk of communicable disease 
transmission.  These violations relate to donor screening and record keeping practices relevant to 
risk factors for, or clinical evidence of, relevant communicable disease agents and diseases.  Title 
21 CFR 1271.150(c)(1) is designed to help ensure that these and other violative practices do not 
occur. 
 
 
III.  DISCUSSION 
 
A.  Am I Responsible for Ensuring that Establishments that I Have 
Manufacturing Arrangements with are in Compliance with CGTP 
Requirements? 
 
Yes.  If you engage another establishment to perform for you any step in manufacture, 
that establishment must comply with requirements applicable to that manufacturing step 
(21 CFR 1271.150(c)(1)(i) and (ii)).  Under 21 CFR 1271.150(c)(1)(iii), before entering 
into a contract, agreement, or other arrangement with another establishment to perform 
for you any step in manufacture, you must ensure that the establishment complies with 
applicable CGTP requirements.  If, during the course of this contract, agreement, or other 
arrangement, you become aware of information suggesting that the establishment may no 
longer be in compliance with such requirements, you must take reasonable steps to ensure 
the establishment complies with those requirements.  If you determine that the 
establishment is not in compliance with those requirements, you must terminate your 
contract, agreement, or other arrangement with the establishment. 
 
B.  What Additional Information would be Helpful to Me in Understanding My 
Responsibilities for Manufacturing Arrangements? 
 
In the preamble to 21 CFR Part 1271, the final rule for CGTPs (Ref. 1), at comments 28 
through 30,1 we discuss several approaches that might be helpful to you if you engage 
another establishment to perform for you manufacturing steps.  As we discussed in the 
preamble, those include the following: 
 
  You should choose carefully establishments with whom you have 
manufacturing arrangements; 
                                                 
1 69 Federal Register 68612 at 68622-3. 
2  Contains Nonbinding Recommendations 
 
 
  You do not have to validate the processes of an outside establishment that you 
engage to perform for you a manufacturing step (e.g., a firm that performs 
terminal sterilization such as irradiation on HCT/Ps for a processor).  That 
establishment is itself subject to the regulations in 21 CFR Part 1271.  
However, you are required to enter into and maintain such arrangements only 
with establishments that comply with applicable CGTP requirements; 
 
  We note that there are many ways of performing the due diligence necessary 
when entering into a manufacturing arrangement with another establishment.  
An initial audit is one method.  Other ways of learning about another 
establishment before you enter into an arrangement with that establishment 
might include reviewing test kit package inserts and a testing laboratorys 
standard operating procedures, and reviewing the establishments compliance 
history.  If you enter into an arrangement with an establishment that does not 
have a compliance history, review of that establishments standard operating 
procedures might assist you in ascertaining that entitys compliance status; and 
 
  Although we recognize the usefulness of an initial audit before entering into an 
arrangement with another establishment, we note that an initial audit would not 
satisfy this requirement throughout the term of a continuing relationship.  
Under 21 CFR 1271.150(c)(1)(iii), you may not ignore information that 
indicates that a company that performs work for you is not in compliance with 
applicable CGTP requirements.  For example, if you have reason to suspect 
that an establishment performing work for you is not in compliance with those 
requirements, you would need to take appropriate action and determine 
whether the establishment is still in compliance with CGTP.   
 
 
IV.  SUMMARY 
 
As described above, this guidance is intended to ensure that you, an establishment that 
manufactures HCT/Ps, fully comply with 21 CFR 1271.150(c)(1) if you enter into a contract, 
agreement, or other arrangement with a contracting establishment to perform for you any step in 
manufacture (Ref. 1).  Your activities to ensure that contracting establishments comply with 
applicable CGTP requirements can help identify and prevent problems such as those noted 
during recent FDA investigations.  Your actions will help prevent undue risks to patient safety.  
 
 
V.  REFERENCES  
  
1.  Current Good Tissue Practice for Human Cell, Tissue, and Cellular and Tissue-Based 
Product Establishments; Inspection and Enforcement - Final Rule (69 Federal Register 
68612, November 24, 2004). 
3