UK MHRA Aims To Address "Fundamental Failures" In Data Integrity

The UK MHRA's revised guidance on maintaining the integrity of data throughout the chemical and pharmaceutical development lifecycle is intended to address various shortcomings identified by regulators during inspections.

The UK Medicines and Healthcare products Regulatory Agency is inviting feedback on an updated guideline on data integrity issues, which has been substantially revised in scope to cover all aspects of pharmaceutical development and good laboratory practice studies regulated by the agency.

Also, the updated document addresses some gaps in the previous version of the guideline and clarifies expectations where inspections showed "an unexpected interpretation of the [MHRA's] requirements," the agency said in a related blog post.

The MHRA told the Pink Sheet that during inspections it had identified instances of companies having misunderstood or misinterpreted the earlier version of its guidance, such as:

• Data reviews performed by companies were not always effective due to lack of understanding of metadata, data lifecycle, data criticality and data risk.
• There remained a belief that a printout from a computerized system was raw data, particularly if the system had been validated.
• There were reports of companies misinterpreting guidance relating to the "primary record" by taking a sub-set of data.

The agency explained that the updated guideline "addresses fundamental failures" identified by the MHRA and international regulatory partners during good laboratory, clinical, manufacturing and distribution inspections; many of which have resulted in regulatory action.

Comments on the revised guideline will be accepted until Oct. 31

Data Integrity Not Limited To GMP

The earlier version of the MHRA's guidance – issued around 18 months ago – was limited in scope as it outlined data integrity expectations only with respect to good manufacturing practice requirements. (Also see "UK MHRA outlines data integrity expectations for pharma industry " - Pink Sheet, 28 Jan, 2015.)

The revised guidance covers all GxP sectors, i.e., good laboratory practice, good clinical practice, good manufacturing practice, good distribution practice and good pharmacovigilance practice. The MHRA clarified that the revised guideline should be read in conjunction with the applicable regulations and the general guidance specific to each GxP.

The updated document also provides additional guidance regarding the design of data governance systems based on quality risk management principles. This will enable drug companies to prioritize deployment of resources to areas of greatest risk, and will also reduce burden, an MHRA spokesperson told the Pink Sheet.

"There is also further advice relating to a focus on the business process (e.g., each production step, or product analysis). This enables a greater understanding of data integrity risks and the control measures required. The guidance promotes the importance of understanding the criticality and risk associated with data generated by that process. With this understanding, companies can design proportionate data integrity controls," the spokesperson added.

The UK-based pharmaceutical industry association ABPI said that the revised guidance "contains a number of amendments" compared with the previous version of the document, which have been made to accommodate the expanded scope of the updated guideline. "The ABPI will review the new draft and, in the light of comments received from member companies, will develop a response to the consultation by the due date," ABPI's Head of Quality and Environmental Standards, Mike Murray, told the Pink Sheet.

Murray noted that the MHRA is a "leading thinker" in this area and its earlier guidance on data integrity had stimulated wider discussions on this topic; it was also well received by industry in the UK and throughout Europe. (Also see "UK MHRA sets ever greater store by data integrity" - Pink Sheet, 21 Apr, 2015.)

The MHRA, for its part, said it supports international convergence on this front as it helps outline common expectations for industry. Also, international convergence would enable regulators to work together more effectively by facilitating information sharing and supervision of the global pharmaceutical development and supply chains.

To this end, the MHRA said it has supported the European Medicines Agency's inspectors working group and the World Health Organization in preparing regulatory guidance on data integrity. (Also see "WHO Tackles Submission Of Insufficient Or False Data By Pharma" - Pink Sheet, 13 Jun, 2016.)

In addition, the MHRA, with its colleagues in the Australian Therapeutic Goods Administration, is co-chairing a data integrity working group within the international pharmaceutical inspection convention and co-operation scheme (PIC/S). (Also see "China Looks For GMP Gaps As It Preps For PIC/S Application" - Scrip, 16 Jun, 2015.)

The PIC/S data integrity group has representatives from 14 authorities spread across four continents, and has been working to produce guidance for participating inspectorates. For this, it is developing existing convergent requirements into a harmonized approach to data integrity in the context of GMP and GDP inspections.

From the editors of Scrip of Regulatory Affairs.