SOURCE: Cutting Edge Information

Cutting Edge Information

January 13, 2016 10:30 ET

Quality Control Challenges Add Up to the Greatest Amount of Regulatory Infractions

Twenty-two of 27 Commercial Trial Sponsors Incurred at Least One Major Trial Master File-based Regulatory Finding

RESEARCH TRIANGLE PARK, NC--(Marketwired - January 13, 2016) - Fulfilling trial master file (TMF) oversight activities is a critical process for clinical operations teams. If external inspections determine that company-managed files do not adhere to industry standards, sponsors risk incurring steep regulatory penalties. According to life sciences intelligence firm Cutting Edge Information, the greatest amount (25 percent) of major infractions for UK-based companies was due to quality systems issues.

In 2014 the UK's Medicines and Healthcare products Regulatory Agency (MHRA) released a report on trial master file-related violations. The report found that, of the 27 commercial trial sponsors that received any type of regulatory inspection, 22 incurred at least one major infraction. According to the MHRA, the majority of major infractions for commercial sponsors occurred in quality systems. A recent reflection paper published by the European Medicines Agency (EMA) echoes these findings. 

Preparing for external regulatory inspections may necessitate additional TMF standard operating procedures (SOPs), stronger quality control processes and new technologies. For example, SOPs for trial master file management dictate the percentage of site- and sponsor-level documents that must undergo quality control checks, as well as the frequency with which documents are reviewed. Additional SOPs cover a myriad of TMF topics, including:

  • Set-up and maintenance standards
  • Ownership of specific documents
  • Expected format and content of documents
  • Archive locations for each TMF

"While important, SOP adherence may prove troublesome for some teams, particularly those that are under-resourced," said Sarah Ray, senior research analyst at Cutting Edge Information. "Part of the difficulty associated with collecting, organizing and archiving TMF materials owes to the attention -- and required resources -- that companies assign to TMF management."

Cutting Edge Information's new TMF white paper, Ensuring Compliant TMF Practices: Common Regulatory Inspection Pitfalls and How to Avoid Them, provides a series of recommendations to help pharmaceutical and medical device teams fine-tune their TMF management operations. Download this free white paper at

Related Report by Cutting Edge Information

Trial Master File Management: Uphold Documentation Processes to Safeguard Good Clinical Practices examines existing TMF practices, such as the scope of teams' involvement, best practices for TMF oversight and quality control activities and companies' transitions from paper-based to eTMF platforms. Industry executives from various functions, including TMF, compliance, quality management and clinical operations can use this report to:

  • Create standardized operating procedures to guide quality control efforts before finalizing trial master files
  • Develop TMF milestones to ensure timely document submissions
  • Convert paper TMF documents into electronic formats to keep pace with industry projections

Please visit to download a TMF Management report summary.

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