Description
This guidance provides recommendations to applicants to aid the development, validation, and use of near infrared (NIR)-based analytical procedures in evaluating the identity, strength, quality, purity, and potency of drug substances and drug products. The recommendations apply to new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplemental NDAs and ANDAs for small molecule drugs. The principles in this guidance also apply to drug substances and drug products covered in Type II drug master files. FDA intends to issue recommendations specific to NIR methods used for biological products under biologics license applications in a future revision to this guidance. This guidance provides recommendations to applicants for applying the concepts described in the guidance for industry PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance (September 2004) (PAT guidance) and the International Council for Harmonisation (ICH) guidance for industry Q2(R1) Validation of Analytical Procedures: Text and Methodology (November 2005) to NIR analytical procedures that use chemometric models. This guidance also provides recommendations for submitting NIR documentation in applications.
Scope & Applicability
Product Classes
4Guidance is applicable to drug and biological products
formaldehyde as a drug product impurity
Applies to drug products including small molecule drugs; assessment of immunosuppression risk
development program for drug and biological products
Stakeholders
1Entity submitting development data and knowledge; Entity performing the work process for change
Regulatory Context
Attributes
7A quality attribute of the spectral acquisition.
Measured using NIR results
Performance characteristic to be validated
Closeness of agreement between a series of measurements from multiple samplings.; Performance characteristic measured by intermediate precision; Performance characteristic to be validated
Performance characteristic assessed via linearity experiment
Evaluation of robustness and parameter ranges of analytical procedures; Development of a robust multivariate analytical procedure includes scientifically justified sample selection; Capacity of an analytical procedure to meet performance criteria during normal use.; Assessed using retention time models; Performance characteristic to be validated
Ability to detect intended mechanism of action without interference; Performance characteristic to be validated
Related CFR Sections (10)
- 21CFR314.70§ 314.70 Supplements and other changes to an approved NDA.
(a) Changes to an approved NDA.Read full regulation →
- 21CFR211.166§ 211.166 Stability testing.
(a) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include:Read full regulation →
- 21CFR211.22§ 211.22 Responsibilities of quality control unit.
(a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no eRead full regulation →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR211.180§ 211.180 General requirements.
(a) Any production, control, or distribution record that is required to be maintained in compliance with this part and is specifically associated with a batch of a drug product shall be retained for at least 1 year after the expiration date of the batch or, in the case of certain OTC drug products lRead full regulation →
- 21CFR211.100§ 211.100 Written procedures; deviations.
(a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures shall include all requirements in this subpart. These written procedures, inRead full regulation →
- 21CFR211.68§ 211.68 Automatic, mechanical, and electronic equipment.
(a) Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinelyRead full regulation →
- 21CFR211.110§ 211.110 Sampling and testing of in-process materials and drug products.
(a) To assure batch uniformity and integrity of drug products, written procedures shall be established and followed that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such control procedures shall be establiRead full regulation →
- 21CFR211.165§ 211.165 Testing and release for distribution.
(a) For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Where sterility and/or pyrogen testing are conducted on sRead full regulation →
- 21CFR211.160§ 211.160 General requirements.
(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted Read full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Positron Emission Tomography (PET) Drugs/Adulterated
3D Imaging Drug Design and Development LLC
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
See Also (8)
- Format and Content for the CMC Section of an Annual Report (Status: Final)
- PAC-ATLS: Postapproval Changes - Analytical Testing Laboratory Sites: Guidance for Industry (Status: Final)
- Medication Guides — Adding a Toll-Free Number for Reporting Adverse Events (Status: Final)
- CMC Postapproval Manufacturing Changes To Be Documented in Annual Reports (Status: Final)
- Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products — Content and Format Guidance for Industry (Small Entity Compliance Guide) (Status: Final)
- Product Identifiers under the Drug Supply Chain Security Act - Questions and Answers: Guidance for Industry (Status: Final)
- Fixed-Combinations and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment or Prevention of Human Immunodeficiency Virus-One Under the President’s Emergency Plan for Acquired Immunodeficiency Syndrome Relief (Status: Draft)
- Annual Reportable Labeling Changes for New Drug Applications and Abbreviated New Drug Applications for Nonprescription Drug Products (Status: Draft)