3 Comments on BA/BE Data Integrity Guidance

The Association for Accessible Medicines (AAM) says it appreciates that FDA is issuing a draft guidance on achieving and maintaining data integrity for the clinical and bioanalytical portions of bioavailability and bioequivalence studies submitted to support INDs, NDAs, ANDAs, the bioanalytical portion of clinical pharmacologic studies supporting CDER-regulated biosimilar applications, and the bioanalytical portion of nonclinical studies included in these types of applications. “It is critical that such study data [are] accurate, complete, and reliable so as to allow FDA to conduct a meaningful substantive review of the data, and to that end it is also critical for applicants and testing sites to have appropriate systems in place to ensure the accuracy, completeness, and reliability of such data throughout the data lifecycle,” the association comment letter says.

AAM says it believes the guidance can be improved in several respects before it is finalized and suggests that in the draft’s recommendations for applicants, FDA should:

• further consider the applicability of certain draft guidance recommendations on quality systems for data integrity;
• acknowledge the QMS (quality management system) expectations since different types of testing sites may vary;
• clarify its expectations for agreements by testing sites to comply with FDA requirements;
• clarify its expectations and recommendations for testing site reporting structure and transparency;
• clarify that applicants may contract with a third party to audit testing sites;
• provide further clarification on what levels of monitoring are appropriate depending on the type of study;
• clarify how applicants may demonstrate a testing site data integrity auditor’s understanding of testing site characteristics; and
• clarify that FDA will treat data integrity monitoring plan audit reports under the FDA Compliance Policy Guide.

For the draft’s comments on recommended elements for a data integrity quality management system, AAM says FDA should:

• move the definition of Computer or Related Systems within the draft to avoid potential confusion;
• recommend study data be archived within four weeks of study completion, rather than within two weeks; and
• clarify that it is generally appropriate to provide auditors with shared, read-only user accounts.

In its comment, Bristol Myers Squibb commends the agency for publishing the draft and makes specific line-by-line recommendations.

The Society of Quality Assurance submits 14 pages of suggested wording changes with its rationale for each change.