FDA 发布人用细胞和基因治疗产品 BLA 的 CMC 灵活性定稿指南
FDA Final: Chemistry, Manufacturing, and Controls Flexibilities for Developing Human Cellular and Gene Therapy Products for a Biologics License Application: Guidance for Industry
FDA 发布人用细胞和基因治疗（CGT）产品 BLA 的 CMC 灵活性定稿指南，按 21 CFR 10.115(g)(4)(i) 即刻实施，文件为 CBER 发布的正式指南。
该定稿指南汇总 CGT 产品在临床开发、工艺验证和商业化放行标准上的 CMC 灵活性安排，便于申请人对照自身开发阶段定位可与 FDA 讨论的事项。
FDA guidance: Chemistry, Manufacturing, and Controls Flexibilities for Developing Human Cellular and Gene Therapy Products for a Biologics License Application: Guidance for Industry
Status: Final. Guidance contains nonbinding recommendations unless applicable laws or regulations are cited.
FDA directory issue date: 2026-05-05 (MM/DD/YYYY in source).
Directory modification time is retained in source metadata; it is not a new issue date or proof that the PDF was revised.
Products: Biologics
Topics: Chemistry, Manufacturing, and Controls (CMC), Gene Therapy
Issuing offices: Center for Biologics Evaluation and Research
Document type: Guidance Document
Official detail page: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-controls-flexibilities-developing-human-cellular-and-gene-therapy
Scope: public guidance PDFs from FDA's whole-agency directory, explicitly tagged Drugs/Biologics and manufacturing/quality/ICH-Quality. The complete PDF follows.
PDF 文字版；图形和原始排版请参阅官方 PDF。
第 1 页
Chemistry, Manufacturing, and
Controls Flexibilities for Developing
Human Cellular and Gene Therapy
Products for a Biologics License
Application
Guidance for Industry
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 one set of either electronic or written comments on this
guidance at anytime. Submit electronic comments to https://www.regulations.gov. Submit
written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You should identify all comments with
docket number FDA-2026-D-4692.
Additional copies of this guidance are available from the Office of Communication, Outreach
and Development (OCOD), by calling 1-800-835-4709 or 240-402-8010, or email
[email protected], or from the Internet at https://www.fda.gov/vaccines-blood-
biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.
For questions on the content of this guidance, contact OCOD at the phone numbers or email
address listed above.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
May 2026
第 2 页
Contains Nonbinding Recommendations
Table of Contents
I. INTRODUCTION..................................................................................................1
II. BACKGROUND ....................................................................................................2
III. FLEXIBLE APPROACHES FOR CMC DEVELOPMENT ............................3
A. Flexibilities During Clinical Development ...................................................................... 3
B. Process Validation Flexibilities ........................................................................................ 5
C. Commercial Specification Flexibilities ............................................................................ 6
D. Additional Flexibilities ...................................................................................................... 7
i
第 3 页
Contains Nonbinding Recommendations
1 Chemistry, Manufacturing, and Controls Flexibilities for
2 Developing a Human Cellular and Gene Therapy Product for a
3 Biologics License Application
4
5
6 Guidance for Industry
7
8
9 This guidance represents the current thinking of the Food and Drug Administration (FDA or
10 Agency) on this topic. It does not establish any rights for any person and is not binding on FDA
11 or the public. You can use an alternative approach if it satisfies the requirements of the
12 applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff
13 responsible for this guidance as listed on the title page.
14
15
16 I. INTRODUCTION
17
18 This guidance describes how FDA applies flexibility to the chemistry, manufacturing, and
19 controls (CMC) requirements for human cellular and gene therapy (CGT) 1 products being
20 developed for biologics license applications (BLAs) under Title 21 of the Code of Federal
21 Regulations (CFR) Part 601 (21 CFR 601). 2 Consistent with the statutory and regulatory
22 requirements for biological products, FDA uses a flexible approach to ensuring applicable CMC
23 requirements are met for CGT products. FDA’s flexible approach serves to help expedite
24 development, review, and patient access to safe and effective CGT products to treat serious or
25 life-threatening conditions that represent significant unmet medical needs.
26
27 FDA has issued several guidances that provide CMC recommendations to sponsors developing
28 CGT products. 3 Sponsors developing CGT products should consider the CMC recommendations
29 in this guidance in addition to those guidances for industry, as applicable. This guidance
30 provides information on when CMC flexibilities may be appropriate for the development of CGT
31 products and does not comprehensively address the CMC information and data necessary to
32 support CGT product licensure under section 351 of the Public Health Service Act (42 U.S.C.
33 262).
34
1
In this guidance, the term cellular and gene therapy (CGT) product refers collectively to cellular therapy and gene
therapy products. These products meet the definition of “biological product” in section 351(i) of the Public Health
Service Act (PHS Act) (42 U.S.C. 262(i)).
2
While this guidance specifically focuses on CMC flexibilities for a CGT product biologics license application,
FDA may consider extending some of the flexibilities to manufacturing supplements submitted post-licensure.
3
For guidances related to chemistry, manufacturing, and controls (CMC) for sponsors developing cellular and gene
therapy products, check the FDA Cellular and Gene Therapy web page at https://www.fda.gov/vaccines-blood-
biologics/biologics-guidances/cellular-gene-therapy-guidances.
1
第 4 页
Contains Nonbinding Recommendations
35 This guidance applies only to CGT products regulated by the Center for Biologics Evaluation
36 and Research (CBER). This guidance does not apply to animal CGT products regulated by the
37 Center for Veterinary Medicine or to other biological products.
38
39 Sponsors should discuss their approach for CMC development with the relevant review division
40 prior to implementation. 4
41
42 In general, FDA’s guidance documents, including this guidance, do not establish legally
43 enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a
44 topic and should be viewed only as recommendations, unless specific regulatory or statutory
45 requirements are cited. The use of the word should in Agency guidances means that something
46 is suggested or recommended, but not required.
47
48
49 II. BACKGROUND
50
51 Many CGT products are innovative biological products that show promise in providing
52 treatments for a wide range of serious or life-threatening conditions in patients with significant
53 unmet medical need such as cancers, genetic disorders, and chronic illnesses. As such, CGT
54 products may be eligible for expedited programs 5 (e.g., fast track designation, breakthrough
55 therapy designation, regenerative medicine advanced therapy designation, 6 priority review
56 designation, accelerated approval 7, platform technology designation 8) to facilitate the
57 development and review of these products and to help ensure their readiness for licensure and
58 availability to patients. However, FDA also recognizes that challenges still exist for sponsors
59 developing safe, effective, and high-quality CGT products when using traditional product
60 development strategies. Some of these challenges include product complexity, patient-specific
61 manufacturing, sophisticated processes and advanced technologies, limited patient population
4
For information on formal meetings between FDA and sponsors or applicants relating to the development and
review of a CGT product, see the draft guidance for industry Formal Meetings Between the FDA and Sponsors or
Applicants of PDUFA Products (September 2023), available at https://www.fda.gov/media/172311/download.
When final, this guidance will represent FDA’s current thinking on this topic.
5
For additional information regarding FDA’s policies and procedures for programs intended to facilitate and
expedite development and review of drugs, see the guidance for industry Expedited Programs for Serious
Conditions – Drugs and Biologics (May 2014)(“Expedited Programs 2014 Guidance”), available at
https://www.fda.gov/media/86377/download.
6
For additional information regarding expedited programs for regenerative medicine therapies for serious
conditions, see the draft guidance for industry Expedited Programs for Regenerative Medicine Therapies for Serious
Conditions (September 2025), available at https://www.fda.gov/media/188874/download. When final, this guidance
will represent FDA’s current thinking on this topic.
7
For additional information regarding FDA’s policies and procedures for accelerated approval, see the draft
guidance for industry Accelerated Approval – Expedited Program for Serious Conditions (December 2024),
available at https://www.fda.gov/media/184120/download. When final, this guidance will represent FDA’s current
thinking on this topic.
8
For additional information regarding FDA’s Platform Technology Designation Program, see the draft guidance for
industry Platform Technology Designation Program for Drug Development (May 2024), available at
https://www.fda.gov/media/178938/download. When final, this guidance will represent FDA’s current thinking on
this topic.
2
第 5 页
Contains Nonbinding Recommendations
62 size, fewer manufacturing runs, product characterization and analytical testing, and short product
63 shelf-life necessitating a narrow window of time from production to administration.
64
65 FDA has gained considerable experience with CGT products and has identified and implemented
66 flexibilities within FDA’s regulations 9 that accommodate the unique characteristics of these
67 innovative therapies, while maintaining rigorous quality standards. FDA is issuing this guidance
68 to help clarify FDA’s use of CMC flexibilities, to inform sponsors, and to facilitate the
69 development of safe, effective, and high-quality CGT products in preparation for a BLA
70 submission.
71
72
73 III. FLEXIBLE APPROACHES FOR CMC DEVELOPMENT
74
75 FDA encourages sponsors of CGT products to consider the principles in this section when
76 pursuing CMC development of products for potential licensure under a BLA. To meet the
77 statutory requirement for licensure, sponsors must demonstrate that their CGT product meets the
78 applicable requirements to ensure that it is safe, pure, and potent. 10 However, FDA recognizes
79 that the unique nature of a CGT product and its development program may require a non-
80 traditional approach to satisfy these requirements.
81
82 FDA considers the following CMC approaches to be appropriate for sponsors to support CGT
83 product development. 11 The extent of the CMC data necessary and the suitability of a CMC
84 flexibility may vary depending on the stage of development, the manufacturing process, and the
85 product. 12 For sponsors considering pursuing a BLA, FDA may seek additional data and
86 information on a case-by-case basis to ensure that the requirements for licensure can be met.
87 Sponsors are strongly encouraged to engage with FDA early and throughout CGT product
88 development.
89
90 A. Flexibilities During Clinical Development
91
92 Sponsors of CGT products should consider the following approaches for CGT product
93 development during clinical investigations:
94
95 • Implementing phase-appropriate current good manufacturing practice (CGMP). In
96 general, the production of an investigational drug 13 for use in a Phase 1 clinical trial is
97 exempt from compliance with the regulations in 21 CFR Part 211. 14 This exemption
98 generally applies to studies that are designed to establish basic safety, rather than the
99 efficacy of the drug product.
100
9
See 21 CFR Part 312 ‒ Investigational New Drug Application, 21 CFR 610 ‒ General Biological Product
Standards, and 21 CFR Part 211 ‒ Current Good Manufacturing Practice for Finished Pharmaceuticals.
10
See section 351(a)(2)(C) of the FD&C Act and 21 CFR 601.2(d).
11
The flexible CMC development approaches provided in this section are not an exhaustive list of those that FDA
may consider appropriate to support CGT product development.
12
See the Expedited Programs 2014 Guidance.
13
In this guidance, the term drug refers to human drug products and biological products.
14
21 CFR 210.2(c).
3
第 6 页
Contains Nonbinding Recommendations
101 For example, FDA encourages the use of a phase-appropriate process control strategy and
102 does not expect process validation for investigational products. However, we
103 recommend that sponsors perform studies to characterize their manufacturing process
104 throughout clinical development. This approach helps sponsors gain knowledge to
105 implement an effective process control strategy, which will facilitate consistent
106 performance of the commercial manufacturing process.
107
108 • Developing release acceptance criteria that are consistent with the phase of the
109 investigational studies. FDA may accept relatively permissive criteria for the release of
110 early-stage investigational CGT products if such criteria do not compromise safety.
111 Sponsors should refine the product specification as additional experience is gained
112 through clinical and product characterization studies. Prior to initiating Phase 2 or 3
113 clinical investigations on the CGT product, release tests must have predefined acceptance
114 criteria. 15,16 FDA recommends sponsors to discuss with FDA the timeline for finalizing
115 release expectations in the investigational process, and when to establish numerical
116 release acceptance criteria in connection with clinical studies intended to provide
117 substantial evidence of effectiveness to maintain product quality and to ensure that a
118 consistently manufactured product is administered during all phases of clinical
119 investigation. 17
120
121 • Using a risk-based approach to comparability studies. The manufacturing and control
122 of CGT products may present challenges due to limitations such as limited process
123 knowledge, limited product quantities, and complex manufacturing processes, which pose
124 a higher risk to product quality than conventional biological products. As such, FDA
125 recommends performing a risk assessment for all manufacturing changes to determine the
126 impact on product quality. For an investigational product, in circumstances where FDA
127 considers a manufacturing change to be minor and with a low risk to product quality,
128 FDA may accept limited comparability data if the CGT product quality attributes are met
129 and the changes are submitted prior to administering the post-change product. 18
130
131 • Leveraging prior knowledge and experience to facilitate CMC development. The
132 amount of knowledge available to support multiple aspects of CGT product development
15
For recommendations regarding CGT product release testing, see the draft guidance for industry Frequently Asked
Questions — Developing Potential Cellular and Gene Therapy Products (November 2024), available at
https://www.fda.gov/media/183631/download. When final, this guidance will represent FDA’s current thinking on
this topic.
16
21 CFR 211.165(d).
17
For recommendations for phase appropriate acceptance criteria, see the guidance to industry Chemistry,
Manufacturing, and Control Information for Human Gene Therapy Investigational New Drug Applications (January
2020), available at https://www.fda.gov/media/113760/download, and the draft guidance for industry Potency
Assurance for Cellular and Gene Therapy Products (December 2023), available at https://
www.fda.gov/media/175132/download. When final, this guidance will represent FDA’s current thinking on this
topic.
18
For recommendations regarding product comparability and management of manufacturing changes for
investigational and licensed CGT products, see the draft guidance for industry Manufacturing Changes and
Comparability for Human Cellular and Gene Therapy Products (July 2023)(“Manufacturing Changes and
Comparability for CGT Products Draft Guidance”), available at https://www.fda.gov/media/170198/download.
When final, this guidance will represent FDA’s current thinking on this topic.
4
第 7 页
Contains Nonbinding Recommendations
133 increases as more CGT products are developed. The Agency may consider proposals
134 submitted to FDA with appropriate justification to leverage CMC knowledge across
135 similar CGT products and, if applicable, critical components 19, such as analytical
136 methods, method validation, lot release specifications 20, stability data, comparability
137 data, and process development and process validation data.
138
139 For example, FDA may consider a sponsor’s use of a platform analytical procedure to
140 reduce the qualification and validation burden during clinical development. 21 A platform
141 analytical method, as defined in the March 2024 guidance for industry entitled Q2(R2)
142 Validation of Analytical Procedures, is a method suitable to test quality attributes of
143 different products without significant change to its operational conditions, system
144 suitability, and reporting structure. 22 The appropriateness of applying a platform
145 qualification and validation may depend on the similarity between the test articles. FDA
146 may request a product-specific verification to support the platform qualification and
147 validation if differences are determined to potentially impact method performance.
148
149 • Utilizing voluntary consensus standards for product development and assessment.
150 FDA has established the Standards Recognition Program for Regenerative Medicine
151 Therapies to identify scientifically sound standards that do not conflict with FDA
152 regulations or policy. Using standards can increase regulatory predictability and reduce
153 the amount of documentation needed in a submission. A list of recognized standards and
154 the terms of recognition are available on CBER's website. 23
155
156 B. Process Validation Flexibilities
157
158 Sponsors of CGT products should consider the following CMC approaches for process
159 validation:
160
161 • Developing a process performance qualification (PPQ) strategy that scientifically
19
See the guidance for industry Chemistry, Manufacturing, and Control Information for Human Gene Therapy
Investigational New Drug Applications (January 2020), available at https://www.fda.gov/media/113760/download.
20
In this guidance, a specification is defined as a list of tests, references to analytical procedures, and appropriate
acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. It establishes the set
of criteria to which a drug substance, drug product, or materials at other stages of its manufacture should conform to
be considered acceptable for its intended use. See also the guidance for industry Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological Products (August 1999)(“Q6B Specifications
Guidance”), available at https://www.fda.gov/media/71510/download.
21
Assay qualification involves determining the assay’s performance characteristics (e.g., accuracy, precision,
specificity, and sensitivity). Assay validation should confirm the performance characteristics of the fully-optimized
assay by comparing assay performance during the validation study to appropriate pre-specified acceptance criteria
for accuracy, precision, specificity, and other relevant performance characteristics. See also 21 CFR 211.165(e) and
211.194(a)(2).
22
This type of method would apply to molecules that are sufficiently alike with respect to the attributes that the
platform method is intended to measure.
23
See the FDA website on Standards Development for Regenerative Medicine Therapies at
https://www.fda.gov/vaccines-blood-biologics/standards-development-regenerative-medicine-therapies, and see also
the guidance for industry Voluntary Consensus Standards Recognition Program for Regenerative Medicine
Therapies (October 2023), available at https://www.fda.gov/media/159237/download.
5
第 8 页
Contains Nonbinding Recommendations
162 supports the number of PPQ batches submitted to the BLA. PPQ is a critical step in
163 validating the performance of a commercial manufacturing process and sponsors are
164 expected to include PPQ data in their BLA submission. FDA acknowledges that
165 sponsors of CGT products may experience PPQ production limitations. FDA uses a
166 flexible, scientific, and risk-based approach to help expedite CGT product development.
167 FDA does not specify a minimum number of PPQ batches in the biologics licensing
168 requirements 24 or CGMP regulations. 25 As such, FDA recommends that sponsors justify
169 the appropriate number of PPQ batches based on context-specific factors, such as the
170 overall level of understanding of the product and process, complexity of the
171 manufacturing process, and levels of control in place. 26 Sponsors should document the
172 studies performed during the design of the manufacturing process and the control
173 strategy, and any relevant manufacturing experience from other sufficiently similar
174 products and processes, in the BLA.
175
176 • Releasing PPQ batches for clinical or commercial distribution. When PPQ
177 production limitations exist, FDA may consider a flexible approach for the completion of
178 PPQ studies post-licensure. A PPQ protocol can be designed to release a PPQ batch for
179 distribution before complete execution of the protocol steps and activities. 27 FDA may
180 consider allowing concurrent release of PPQ batches for commercial use after BLA
181 approval if the batches meet the commercial release specification and are within the
182 commercial shelf life. In addition, any such batches that meet the phase-appropriate
183 release criteria established under an IND may be used for a clinical investigation.
184
185 C. Commercial Specification Flexibilities
186
187 Sponsors of a CGT product should consider the following CMC approaches for establishing a
188 commercial specification when pursuing submission of a BLA:
189
190 • Developing product release strategies consistent with the nature of the product, the
191 manufacturing process, and the number of lots available at the time of BLA
192 submission. FDA recognizes that there may be situations where only a small number of
193 CGT product lots are available for analysis at the time of BLA submission, often due to
194 the inherently small patient population. In these circumstances, when appropriate and
195 while still ensuring product quality, FDA may consider flexible approaches for
196 establishing product release specifications when it is not feasible to define statistically
24
21 CFR 601.20.
25
See, e.g., 21 CFR 211.100 and 21 CFR 211.110.
26
FDA encourages sponsors who are preparing to validate the manufacturing process of a CGT product to contact
FDA to discuss their validation strategy before implementation. For more information regarding the general
principles and approaches that FDA considers appropriate elements of process validation for the manufacture of
biological products, see the guidance for industry Process Validation: General Principles and Practices (January
2011)(“Process Validation Guidance”), available at https://www.fda.gov/media/71021/download. See also the
guidance for industry Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients
(September 2016), available at https://www.fda.gov/files/drugs/published/Q7-Good-Manufacturing-Practice-
Guidance-for-Active-Pharmaceutical-Ingredients-Guidance-for-Industry.pdf.
27
For more information and recommendations regarding concurrent release for process performance qualification
(PPQ) batches, see Section V of the Process Validation Guidance.
6
第 9 页
Contains Nonbinding Recommendations
197 robust commercial acceptance criteria at the time of initial approval.
198
199 • Developing a scientifically supported analytical method validation strategy. For
200 validation of analytical methods used for release testing, FDA does not specify a
201 minimum number of lots to be used in the validation study. FDA may consider analytical
202 method validations using a single representative lot, when appropriate. FDA may
203 consider such a strategy if it is scientifically supported and the relevant data submitted to
204 FDA demonstrates the method to be sufficiently robust and suitable for its intended
205 use. 28,29
206
207 • Leveraging post-approval manufacturing experience to ensure robust commercial
208 acceptance criteria. Consistent with FDA’s policies regarding change management of
209 analytical procedures, sponsors can consider discussing with FDA whether it may be
210 appropriate to commit to post-approval reevaluation of product release acceptance criteria
211 in certain circumstances (e.g., when only a small number of CGT product lots are
212 available at the time of BLA submission, and when there are data generated from
213 multiple commercial batches produced after the approval if the manufacture of the CGT
214 product demonstrates consistent product quality). 30 This approach supports the
215 development of more statistically sound acceptance criteria over time. Changes to
216 specifications after approval must be submitted in a prior approval supplement. 31
217
218 D. Additional Flexibilities
219
220 Sponsors of a CGT product should consider the following CMC approaches when pursuing
221 submission of a BLA:
222
223 • Leveraging stability data to support commercial expiration dating. FDA generally
224 recommends that sponsors submit real-time stability data from three lots manufactured at
225 the commercial facility, with a minimum of six months of data. However, FDA may
226 consider an alternative number of stability lots based on a risk evaluation. In addition,
227 sponsors may use stability data from clinical lots if the lots are representative (e.g.,
228 manufactured with the commercial process, using the commercial formulation, and in the
229 commercial container closure). In this case, sponsors should provide sufficient data from
230 the clinical lots to support the product’s shelf life. In addition, sponsors may submit
231 stability data from similar products to be considered for use as supporting data for setting
232 the initial stability period when a concurrent testing strategy is included in the stability
233 testing protocol. For more information related to these recommendations, see the June
28
For more information, see the guidance for industry Q2(R2) Validation of Analytical Procedures (March 2024),
available at https://www.fda.gov/media/161201/download, and the guidance for industry Q14 Analytical Procedure
Development (March 2024), available at https://www.fda.gov/media/161202/download.
29
21 CFR 211.194(a)(2).
30
Under 21 CFR 211.180(e), sponsors must maintain written records to evaluate the quality standards of each drug
product, at least annually, to determine the need for changes in the drug products specifications of manufacturing or
control procedures. Further refinement of acceptance criteria may be warranted if supported by additional
manufacturing experience and data obtained after approval. For more information, see the Q6B Specifications
Guidance.
31
21 CFR 601.12. See also the Manufacturing Changes and Comparability for CGT Products Draft Guidance.
7
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Contains Nonbinding Recommendations
234 2025 draft guidance for industry entitled Q1 Stability Testing of Drug Substances and
235 Drug Products 32; when final, this guidance will represent FDA’s current thinking on this
236 topic.
237
238 • Seeking an exception from FDA for retaining reserve samples. Under most
239 circumstances, a manufacturer of a biologic must retain sufficient material from each lot
240 of product manufactured for six months after the expiration date. 33 However, FDA
241 recognizes that meeting this requirement may not be feasible when CGT product lots are
242 very small or manufactured for individual patients. In such circumstances, FDA may
243 consider exceptions, as appropriate and consistent with 21 CFR 600.13.
244
245 • Using alternative analytical methods in lieu of compendial methods to reduce
246 sample volume or testing time for release of intermediates, drug substance, and
247 drug product lots. Compendial methods have historically been used for some lot release
248 tests of biological products. However, alternative analytical methods with rapid detection
249 capabilities, which often use proprietary and/or novel technologies, may provide more
250 efficient microbiological control and assurance to allow for expedited release of CGT
251 products. As such, FDA may consider the use of an alternative analytical method if
252 sufficient information and data is available to demonstrate that the alternative analytical
253 method meets the appropriate standards of accuracy, sensitivity, specificity, and
254 reproducibility 34 and is validated to be suitable for its intended purpose. 35 For sterility
255 testing, 21 CFR 610.12 allows for the use of different types of test methods, as they
256 become available, to accommodate scientific and technological advancements, provided
257 that they are appropriately validated and verified as provided in the regulation. 36
32
Available at https://www.fda.gov/media/187161/download.
33
21 CFR 600.13.
34
For discussion about the use of noncompendial analytical procedures, see also the guidance for industry
Analytical Procedures and Methods Validation for Drugs and Biologics (July 2015)(“Analytical Procedures and
Methods Validation Guidance”), available at https://www.fda.gov/files/drugs/published/Analytical-Procedures-and-
Methods-Validation-for-Drugs-and-Biologics.pdf. As a holder of the BLA, you must: (1) submit the data used to
establish that the analytical procedures used in testing meet proper standards of accuracy and reliability, and (2)
notify the FDA about each change in each condition established in an approved application beyond the variations
already provided for in the application, including changes to analytical procedures and other established controls.
See 21 CFR 601.2(a), 601.2(c), and 601.12(a); see also 21 CFR 211.165(e). In addition, for a product licensed
under a BLA, if the change is to a procedure prescribed in FDA regulations that change must be approved by FDA
pursuant to 21 CFR 610.9(b).
35
21 CFR 211.194(a)(2). See also the Analytical Procedures and Methods Validation Guidance.
36
See Amendments to Sterility Test Requirements for Biological Products, 77 Fed. Reg. 26162, at 26174 (May 3,
2012).
8
来源：FDA 全域目录：药品／生物制品制造质量指南 · fda.gov