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

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Contains Nonbinding Recommendations 

Guidance for Industry 

Compliance with 21 CFR Part 1271.150(c)(1) – Manufacturing 

Arrangements 

This guidance represents the Food and Drug Administration’s (FDA’s) 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 establishment’s 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. 

FDA’s guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the FDA’s 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 FDA’s guidances means that something is suggested or 

recommended, but not required. 

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Contains Nonbinding Recommendations 

II. BACKGROUND 

FDA’s 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. 

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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 laboratory’s 

standard operating procedures, and reviewing the establishment’s compliance 

history. If you enter into an arrangement with an establishment that does not 

have a compliance history, review of that establishment’s standard operating 

procedures might assist you in ascertaining that entity’s 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). 

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