Questions and answers about data integrity FDA published April 14 as draft guidance could go a long way toward helping drug manufacturers avoid the type of import alerts and warning letters that in recent years have dominated the agency's drug good manufacturing practices enforcement activities.

The percentage of firms placed on drug GMP import alert that have data integrity issues steadily has risen from zero to 56% over the past five years, according to data FDA recently presented ([A#08151022005]).

At the same time, the number of drug GMP warning letters focused substantially on data integrity increased from two in 2010 to 10 in 2014, with another nine in the first eight months of 2015, according to an analysis by "The Gold Sheet" ([A#08151022008]).

However, despite the growing significance of the data integrity issue, manufacturers have had little in the way of FDA regulatory guidance on the topic.

The agency still directs firms to its 1991 Application Integrity Policy, prompted by the generic drug scandal of the late 1980s, for guidance on how to investigate data falsification.

But until now, the agency's best advice on data integrity has been contained in recent warning letters like the one it sent February 2014 to [USV Ltd.], in Mumbai, India, which outlined a seven-step process for investigating data integrity problems.

The "Data Integrity and Compliance With CGMP" draft guidance discusses the issues raised in such warning letters in a question-and-answer format that could be particularly useful in training, said data integrity consultant Monica Cahilly, president, Green Mountain Quality Assurance, in Warren, Vt.

Cahilly said the draft guidance addresses a common failure in industry to see how GMP requirements apply to electronic data. "This lack of understanding seems to have led to many of the data integrity issues being discovered during recent regulatory inspections," she said.

For example, she said some might think that information is not data until they save it, or that they can avoid ensuring the accuracy and reliability of electronic data by calling print-outs raw data.

Cahilly said FDA's draft guidance aligns with March 2015 guidance from the UK Medicines and Healthcare products Regulatory Agency as well as guidance the World Health Organization has drafted ([A#08150326004]).

Meanwhile, she noted, the Pharmaceutical Inspection Cooperation Scheme, or PIC/S, is developing guidance for its member inspectorates.

Cahilly expects cost reductions and efficiency gains as the pharmaceutical industry adheres to the draft guidance, which "will require us as an industry to modernize, to embrace our current technologies and use and control them properly."

Retain Every Scrap Of Paper

When data is generated to satisfy a GMP requirement, it is a GMP record that must be retained, the guidance emphasizes – even if it is numbers jotted on scraps of paper that workers were planning to discard after transcription to a permanent laboratory notebook.

The guidance explains why the agency often cites companies for using actual samples during suitability testing of chromatography and other testing equipment. The agency explained the problem is when companies do this as "a means of testing into compliance" – the practice of testing different samples until obtaining the desired passing result. "We would consider it a violative practice to use an actual sample in test, prep, or equilibration runs as a means of disguising testing into compliance."

Similarly, it is not OK to save only the final results from reprocessed laboratory chromatography, the guidance said. All results should be retained for review, lest the data were reprocessed into compliance.

For equipment like pH meters and balances, it's fine to print out data for backup records, the guidance said. But for other equipment like Fourier transform infrared spectroscopy systems, static records like print-outs won't suffice. Their spectral files, which can be reprocessed, must be saved. And those files must display the full spectrum.

The guidance clarified that if someone in the company raises a concern about potential data falsification, the company must investigate the concern within its formal quality system rather than handling it informally.

The guidance also clarified data integrity terminology as it relates to requirements in FDA regulations, including metadata, audit trails, backup data, static and dynamic records, and the term "data integrity" itself.

[Editor's note: "The Gold Sheet" also published this article. "The Tan Sheet" brings selected complementary coverage from our sister publications to our subscribers.]

FDA Collates GMP Data Integrity Advice Into Draft Guidance

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