Description
This guidance is intended to be used as a companion to the guidance Pharmacogenomic Data Submissions (March 2005). It reflects experience gained since the issuance of that guidance with voluntary genomic data submissions as well as with review by the FDA of numerous protocols and data submitted under investigational new drug (IND) applications, new drug applications (NDAs), and biologics license applications (BLAs). The recommendations are intended to facilitate scientific progress in the field of pharmacogenomics and to facilitate the use of pharmacogenomic data in drug development. The FDA believes that the recommendations made in this companion guidance, together with the recommendations in the March 2005 guidance, will benefit sponsors considering the submission of either voluntary genomic data submissions or marketing submissions containing genomics data. As technology changes and more experience is gained, these recommendations may be updated.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3unique issues with adaptive study designs for diagnostic devices; heterogeneous in scope and include devices that may be invasive
Regulatory submission type containing clinical and non-clinical genomic data
there are numerous variables that may affect sample reproducibility in microarray studies.
Stakeholders
2Entity responsible for submitting NDINs
Entity responsible for submitting applications under section 524B
Regulatory Context
Regulatory Activities
5Investigational New Drug submissions
Regulatory pathway for pharmacogenomic data
Information to be included in the genotyping report regardless of submission type.
New Drug Application
Biologics License Application
Document Types
6Reports where sponsors should report protocol deviations
Experimental summary table used to summarize key parameters in a microarray study
SDTM dataset package required for submission.
CSR supported by ADaM datasets; Contains analysis results and animal listings
Section III.C Genotyping Report
SOPs describing the manufacturing process for CSP
Attributes
7ensure quality during isolation and confirm high quality before use
Group characteristic identifier
Statistical parameter for genes of interest
Parameter included in gene list submissions
clearly visible 18S and 28S RNA bands are taken as measure of RNA integrity.
Array QC parameters performed by vendor.
range within which accuracy should be maintained
Technical Details
Substances
9Examples of GT products can include purified nucleic acid such as RNA.
Test material used in exposure domain
Substance used in a 6-day repeated-dose experiment in rats
Example of a drug formulated by activity
Thresholds for concentration, volume, and quality must be justified.
reacting with DNA bases
recommend that the need for adding RNA stabilizing agents to samples/reagents be assessed
Used for cryopreservation storage
the overabundance of globin mRNA can result in failure to detect some transcripts that are of low abundance.
Testing Methods
10Gene expression data from microarrays
used to demonstrate relevance of previous toxicity testing
considerations for irritation and sensitization analysis
Analytical methodology for drug dosing or metabolism
Baseline laboratory assessment for patient enrollment.
Used for MRD measurement and chimerism testing.
Transfer of genomic biomarker sets from microarrays to other platforms such as quantitative RT-PCR.
Section IV. Proficiency Testing
Some commonly used methods include the Ficoll-Hypaque centrifugation
Referenced in American Laboratory regarding standard additions.
Processes
7One of the most critical steps in performing RNA-based experiments; Establishing an upper limit for batch size will reduce problems encountered during the scaling-up process since long processing times can jeopardize RNA integrity.
Scientific process involving raw and normalized gene expression data
Assessment of the overall competence of a facility
Foundation for deriving biological conclusions
We recommend the use of consistent methods of target labeling throughout the particular study
Traditional breeding practice used to create genetic variation.
Include sample processing and labeling details.
Clinical Concepts
10Specific genes sets derived from microarray experiments proposed as genomic biomarkers.
Microscopic finding observation
Organ evaluated for microscopic findings
Alanine aminotransferase clinical pathology test
Clinical pathology test parameter
Specimen type for clinical pathology
Risk associated with long-term therapy requiring monitoring
Safety findings including deaths and post-mortem examinations
Determine whether biological pathways may be of functional relevance to the mechanism of drug action.
RNA can be isolated from whole blood or from peripheral blood mononuclear cells (PBMCs).
Identified Hazards
Hazards
2RNA is sensitive to degradation by RNase
Factors that can result in DNA degradation including nucleases and freeze-thaw cycles.
Standards & References
External Standards
6Minimum Information About a Microarray Experiment guidelines for experimental parameters
Standard for Exchange of Nonclinical Data; Standard for Exchange of Nonclinical Data for toxicology studies.; Standard for Exchange of Nonclinical Data provides structure for nonclinical tabulation datasets; Standard for nonclinical data tabulation; Standard for nonclinical study data; Standard for nonclinical tabulation data; dataset submitted to the FDA for nonclinical trials
Standard for mapping health care data for submission; Study Data Tabulation Model used for clinical data submission
The Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM) specifications provided in this document
Regulatory compliance for information collection
Routine use of standardized scanner reference materials for calibrations.
Specifications
1the ratio of absorbance at 260nm and 280 nm (A260/A280) can be used to assess RNA purity and is typically recommended to be greater than 1.8.
ICH References (1)
document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Mid-Link Testing Company, Ltd
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Sanitation & Environmental Technology Institute dba SDWH
- 2023-10-31
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Samm Solutions, Inc., d.b.a. BTS Research
Related Warning Letters (9)
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Mid-Link Testing Company, Ltd
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Sanitation & Environmental Technology Institute dba SDWH
- 2023-10-31
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Samm Solutions, Inc., d.b.a. BTS Research
- 2022-08-09
Bioresearch Monitoring Program
Valley Biosystems
- 2022-02-22
Good Laboratory Practice (GLP)
Toxikon Corporation/Labcorp Bedford LLC
- 2020-05-05
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
University of Kentucky
- 2020-04-07
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Steiner Biotechnology, LLC
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Evidentiary Expectations for 510(k) Implant Devices: Draft Guidance for Industry and Food and Drug Administration Staff (Status: Draft)
- Redbook 2000: IV.C.9.b. Guidelines for Developmental Toxicity Studies (Status: Final)
- Redbook 2000: IV.C.9.a.Guidelines for Reproduction Studies (Status: Final)
- Redbook 2000: IV.C.5.b. One-Year Toxicity Studies with Non-Rodents (Status: Final)
- Redbook 2000: IV.C.4.b. Subchronic Toxicity Studies with Non-Rodents (Status: Final)
- Redbook 2000: IV.C.4.a. Subchronic Toxicity Studies with Rodents (Status: Final)
- Redbook 2000: IV.C.3.b. Short-Term Toxicity Studies with Non-Rodents (Status: Final)
- Redbook 2000: IV.C.3.a. Short-Term Toxicity Studies with Rodents (Status: Final)