In the pharmaceutical and biotechnology sector, validation is a mandated practice integral to the entire drug development process, particularly in the context of computerized systems and manufacturing testing methodologies. The necessity for validation arises from the regulatory requirements defined by the US Food and Drug Administration (FDA) governing pharmaceutical manufacturing processes under Title 21, Chapter 1, Subchapters C, F and H.
While Title 21 references validation in different parts, the focus of validation in this article will be on the scope of its application in a cultural mindset of Good Manufacturing Practice (GMP). These are some of the regulations for direct manufacturers of pharmaceutical products, thus defined as “manufacturer” in these regulations. These manufacturers (pharmaceutical or biotechnology organizations) have Quality departments that oversee the implementation of the validation standards and processes as part of their regulated business processes.
Validation in quality management systems
Title 21 of the Code of Federal Regulations (CFR) are the regulations for Food and Drugs. Chapter 1 of Title 21 contains 1,299 separate Parts enforced by the FDA, Department of Health and Human Services.
Categorized in Subchapter H for Medical Devices is 21 CFR 820 [Quality System Regulation], which governs the design, manufacture, labeling, storage and servicing of finished devices intended for human use.
In this Part and paragraphs, the following are defined as follows:
§ 820.3 (z) “Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled.”
§ 820.3 (aa) “Verification means confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.”
In this example, a software developer builds a user authentication interface (a user log-in/password dialog). In practical terms, a verification activity would entail a simple test case with screenshot evidence that the dialog window was built according to a defined user requirement or functional specification. A validation activity would entail a formal test case of its functionality and usability, which indicates whether a user can or cannot successfully log in with their credentials (with pass/fail criteria) per the definition in § 820.3 (z)(2)
“Design validation means establishing by objective evidence that device specifications conform with user needs and intended use(s).”
In § 820.3 (z)(1), Process validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.
In quality control (QC) laboratories, the intended use for lab instruments is for data acquisition, and software for data analysis are qualified together as a single entity. The digital transformation of raw data into analyzed reportable results is considered an automated process that requires validation per § 820.70 (i)
“When computers or automated data processing systems are used as part of production or the quality system, the manufacturer shall validate computer software for its intended use according to an established protocol. All software changes shall be validated before approval and issuance. These validation activities and results shall be documented.”
Test methods and procedures from Development groups being introduced into the regulated space require validation before they can be used to assess and release products are regulated per § 820.75(a)
“Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated, shall be documented.”
Validated test methods and procedures that are used in QC must be maintained and monitored per § 820.75(b)
“Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met.(1) Each manufacturer shall ensure that validated processes are performed by qualified individual(s).
(2) For validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented.”
In the course of routine manufacturing, GMP requires proper documentation of deviations per § 820.75(c)
“When changes or process deviations occur, the manufacturer shall…
Read More: Ensuring Regulatory Compliance: The Role of Validation in Pharmaceutical and