What a preclinical final report has to contain

The report is a defined document, not a write-up

A final report must be prepared for each nonclinical laboratory study, and the rule lists what it must include. The list runs to fourteen items, and it opens with a phrase that keeps it a floor rather than a ceiling: the report shall include, but not necessarily be limited to, the following.

Several items are ordinary and appear in any published paper. The name and address of the facility performing the study and the dates it was initiated and completed. The objectives and procedures stated in the approved protocol, including any changes to the original. The statistical methods employed for analysing the data. A description of the methods used. A description of the transformations, calculations or operations performed on the data, a summary and analysis of the data, and a statement of the conclusions drawn from the analysis.

Several are about the material, and connect the report back to the characterization requirements: the test and control articles identified by name, chemical abstracts number or code number, strength, purity, and composition or other appropriate characteristics; and the stability of the articles under the conditions of administration.

Several are about the test system and the exposure: a description of the test system used, including where applicable the number of animals, sex, body weight range, source of supply, species, strain and substrain, age, and the procedure used for identification; and a description of the dosage, dosage regimen, route of administration, and duration.

And several are about accountability, which is where the list stops resembling a journal article. The name of the study director, the names of other scientists or professionals, and the names of all supervisory personnel involved in the study. The signed and dated reports of each of the individual scientists or other professionals involved. The locations where all specimens, raw data and the final report are to be stored. And the statement prepared and signed by the quality assurance unit.

The item with no journal equivalent

One item in the list has no counterpart in the ordinary structure of a scientific paper. The final report must include a description of all circumstances that may have affected the quality or integrity of the data.

It is stated as a required section, not as a disclosure to be made if the authors judge it material. The study director carries the matching duty during the study: to assure that unforeseen circumstances which may affect the quality and integrity of the study are noted when they occur, and that corrective action is taken and documented.

The quality assurance unit's signed statement sits beside it and does a different job. That statement specifies the dates inspections were made and the dates findings were reported to management and to the study director. It is not a certification that the study was good. It is a record that an independent unit looked, and when.

The unit's prior duty gives that statement its weight. Before the report goes out, the unit must review the final study report to assure that it accurately describes the methods and standard operating procedures, and that the reported results accurately reflect the raw data of the study. Somebody who did not run the experiment has compared the report against the underlying records.

Two signatures close the document. The final report must be signed and dated by the study director — and, as the definitions section states, that date is the study completion date. A study is over when its director signs the report, which means the report cannot be finished before the study is.

The protocol that has to exist first

A report is only as constrained as the plan it reports against. Each study must have an approved written protocol that clearly indicates the objectives and all methods for the conduct of the study, and the rule lists twelve items it must contain as applicable.

A descriptive title and statement of the purpose. Identification of the test and control articles by name, chemical abstract number or code number. The name of the sponsor and the name and address of the testing facility. The number, body weight range, sex, source of supply, species, strain, substrain and age of the test system. The procedure for identifying the test system. A description of the experimental design, including the methods for the control of bias.

That last phrase is worth pausing on. Control of bias is a required element of the written protocol, decided in advance, not a discussion point in the paper afterwards.

The remaining items cover the diet and the solvents, emulsifiers and other materials used to solubilise or suspend the articles, with specifications for acceptable contaminant levels; each dosage level with the method and frequency of administration; the type and frequency of tests, analyses and measurements; the records to be maintained; the date of approval by the sponsor and the dated signature of the study director; and a statement of the proposed statistical methods to be used.

The proposed statistical methods are named in the protocol and then reported in the final report. That pairing is the closest thing in these rules to a pre-specification requirement, and it is what makes the report's statistics section auditable rather than merely stated.

Changes are not forbidden, only recorded. All changes in or revisions of an approved protocol, and the reasons for them, must be documented, signed by the study director, dated, and maintained with the protocol. The conduct section then requires simply that the study be conducted in accordance with the protocol and the test systems monitored in conformity with it.

How the underlying data have to be written down

The rule defines raw data before it regulates it. Raw data means any laboratory worksheets, records, memoranda, notes, or exact copies of them, that are the result of original observations and activities of a study and are necessary for the reconstruction and evaluation of the report of that study. It may include photographs, microfilm or microfiche copies, computer printouts, magnetic media including dictated observations, and recorded data from automated instruments.

The recording requirement is specific to the point of being unfashionable, and it is the clearest statement of data integrity in the part. All data generated during the conduct of a study, except those generated by automated data collection systems, must be recorded directly, promptly and legibly in ink. All data entries must be dated on the date of entry and signed or initialled by the person entering the data.

Corrections are governed rather than banned. Any change in entries must be made so as not to obscure the original entry, must indicate the reason for the change, and must be dated and signed or identified at the time of the change.

The automated case is handled in parallel. In automated data collection systems, the individual responsible for direct data input must be identified at the time of input, and any change in automated entries must be made so as not to obscure the original entry, must indicate the reason, must be dated, and the responsible individual must be identified.

Two more requirements attach to the physical material. Specimens must be identified by test system, study, nature and date of collection, and that information must be on the specimen container or accompany the specimen in a manner that precludes error in recording and storage. And records of gross findings for a specimen from post-mortem observations should be available to a pathologist examining that specimen histopathologically — a small clause that exists because a pathologist reading slides blind to the gross findings and a pathologist reading them informed are doing different work.

The archive, the correction mechanism, and the clock

All raw data, documentation, protocols, final reports and specimens generated as a result of a study must be retained, with a stated exception for specimens obtained from mutagenicity tests and wet specimens of blood, urine, faeces and biological fluids.

There must be archives for orderly storage and expedient retrieval of all of it, with storage conditions that minimise deterioration in accordance with the retention period and the nature of the material. A facility may contract with commercial archives. Raw data and specimens may be held elsewhere provided the archives carry a specific reference to those locations. One individual must be identified as responsible for the archives, only authorised personnel may enter, and material must be indexed to permit expedient retrieval.

Correcting a report has one route and it leaves a trace. Corrections or additions to a final report must be in the form of an amendment by the study director. The amendment must clearly identify the part of the report being added to or corrected, give the reasons, and be signed and dated by the person responsible. There is no mechanism for quietly reissuing a report.

The retention clock has three settings and the shortest applies. At least two years following approval of a research or marketing permit application the study supported — except that studies supporting investigational applications are governed by the next rule instead. At least five years following the date the study results are submitted to the agency in support of such an application. Or, where the study is never submitted at all, at least two years following the date the study is completed, terminated or discontinued.

One provision covers the case a reader is most likely to care about, because it is the one that decides whether records survive a company. If a facility conducting nonclinical testing goes out of business, all raw data, documentation and other specified material must be transferred to the archives of the sponsor of the study, and the agency must be notified in writing of the transfer.

None of this describes what a journal requires. A published preclinical paper is a summary written for readers, and it is not obliged to name its study director, list its supervisory personnel, disclose the circumstances that may have affected data quality, carry an independent unit's signed inspection dates, or state where the raw data are stored. That gap is not a defect in any particular paper. It is the difference between a document written to be read and a document written to be audited.

Sources

Each document below is named as it names itself, with the date printed on that document rather than the day it was read.

1. 21 CFR 58.185 — Reporting of nonclinical laboratory study results, read in full for the fourteen required contents of a final report including the description of all circumstances that may have affected data quality or integrity, the requirement that the study director sign and date it, and the amendment-only route for corrections or additions — Electronic Code of Federal Regulations, National Archives and Records Administration, September 2026
2. 21 CFR 58.120 — Protocol, read in full for the twelve required protocol contents including the description of the experimental design with the methods for the control of bias, the contaminant specifications for dietary materials, the dated signature of the study director, the statement of proposed statistical methods, and the documentation of any protocol change — Electronic Code of Federal Regulations, National Archives and Records Administration, September 2026
3. 21 CFR 58.130 — Conduct of a nonclinical laboratory study, read in full for the requirement to record data directly, promptly and legibly in ink with date and signature, the rule that a change must not obscure the original entry and must state its reason, the parallel requirements for automated data collection, the specimen identification requirement, and the availability of gross findings to the pathologist — Electronic Code of Federal Regulations, National Archives and Records Administration, September 2026
4. 21 CFR 58.190 — Storage and retrieval of records and data, read in full for the retention of raw data, documentation, protocols, final reports and specimens, the archive requirements, the commercial archive allowance, the named individual responsible, the restriction on entry and the indexing requirement — Electronic Code of Federal Regulations, National Archives and Records Administration, September 2026
5. 21 CFR 58.195 — Retention of records, read in full for the three retention periods and the shortest-applies rule, the treatment of fragile specimens, and the requirement that a facility going out of business transfer all raw data and documentation to the sponsor's archives with written notice to the agency — Electronic Code of Federal Regulations, National Archives and Records Administration, September 2026
6. 21 CFR 58.3 — Definitions, read for the definition of raw data and its enumerated examples, and for study completion date defined as the date the final report is signed by the study director — Electronic Code of Federal Regulations, National Archives and Records Administration, September 2026