Lack of Scientifically Sound Laboratory Controls often mentioned in FDA 483s Reports

Recommendation

7/8 May 2024

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Observations made by the inspector during an FDA inspection are listed on the FDA Form 483. Spreadsheets summarizing the areas of regulation cited on FDA's system-generated 483s are available by fiscal year on the FDA's homepage in the subsection on "Inspection Observations". These spreadsheets represent the area of regulation and the number of times it was cited as an observation on a Form FDA 483.

General Requirements for Laboratory Controls

In the Code of Federal Regulations (21 CFR Part 211.160), general requirements for laboratory controls are defined: 

Sec. 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 by the appropriate organizational unit and reviewed and approved by the quality control unit. The requirements in this subpart shall be followed and shall be documented at the time of performance. Any deviation from the written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms shall be recorded and justified.
(b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity.

Inspection Observations

According to the current file (fiscal year 2020), 349 corresponding forms were issued in the area of "Drugs". With 58 observations, violations of section 21 CFR 211.160(b) ("Scientifically sound laboratory controls") are on the third place. 

The long Description for this deviation is: "Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity."

Violations of 21 CFR 211.160(a) ("Following/documenting laboratory controls") are also frequently cited, with a total of 31 cases in fiscal year 2020.

779 FDA 483's were issued during the fiscal year 2019, among them 145 violations of section 21 CFR 211.160(b) and 40 violations of section 21 CFR 211.160(a).