Data Integrity: Risks and Solutions

Senior Life Science Consultant


To ensure patient health and product quality, adhering strictly to Good Manufacturing Practice (GMP) is essential. One part of GMP, which is increasing in importance within the last few years due to higher FDA focus, is Data Integrity. Data Integrity means the overall documentation of every GxP-relevant activity performed during the whole product life cycle. The FDA recommends that this documentation should be based on the ALCOA principles. To guarantee Attributable, Legible, Contemporaneous, Original and Accurate documentation, life-science companies increasingly seek experts for advice.

Focusing on data integrity by kicking off respective projects and hiring consulting experts within this field makes sense, taking into account the numerous warnings of authorities that came up recently.

For example, the risk of cross-contaminations in multi-purpose facilities is addressed in a recent warning letter (320-18-08, Bayer Pharma AG): According to 21 CFR 211.67 the removal or obliteration of previous batch identification must be documented.  In audits, written procedures and schedules as well as reports should be present for adequate and professional cleaning and maintenance of equipment used in the manufacture, processing, packing, or holding of a drug product. It should also be considered that not only the equipment but also the room surfaces should have adequate cleaning plans to ensure that powder residues are removed from room surfaces as part of product changeovers.

Furthermore, the management of complaints have recently been addressed by the FDA concerning product quality. Complaints from suppliers or clients must be reported and investigated adequately. Root cause analysis and Corrective and Preventive Actions (CAPAs) must be carried out and documented to always ensure the product quality. According to 21 CFR 211.192, the quality control unit should review all drug product production and control records for determining compliance with all established and approved written procedures before batch release or distribution. In case of any discrepancy of a batch, investigations must be started immediately to avoid further distribution and to determine if other batches are affected. A written record needs to be created of the required investigation including conclusion and follow up for providing traceable complaint management. Following 21 CFR 211.22 the quality control unit shall have the responsibility and authority to review production records as well as to approve or reject all components, drug product containers, closures, in-process materials, packing material, labeling, and drug products. Additionally, personnel training records in original form must be present for ensuring that the quality unit as well as all other employees are capable of performing their assigned functions.

Another aspect, which needs to be considered carefully, is the classification of “GMP“ and “non-GMP“ for activities or equipment. There was a recent deviation at Bayer Pharma AG because parameters of automatically visual inspection analysis used for reject or accept tablets were wrongly defined as “non-GMP“ data. Entering reliable settings into machine programming is part of cGMP. Therefore, careful reassessment is recommended of any system or activity associated with drug manufacturing or testing equipment considered as “non-GMP“.

Another hot topic is the careful observation of audit trails. It must be ensured that all data derived from all tests necessary to assure compliance with established specifications and standards are included in the laboratory records, according to 21 CFR 211.194. It is not compliant to program equipment to exclude values from audit trails, which are out of range or out of interest.

In case of data integrity violations like the ones described in this article, the company is responsible to investigate these violations as soon as possible. Causes must be determined for preventing their recurrence and for preventing other violations in further facilities.

The risk of product ban from the market should be avoided in advance by ensuring all activities and equipment involved in production are compliant with data integrity rules. External consultants can help to implement data integrity projects, which should be planned well and include different facilities as well as different work streams e.g. for production processes, equipment and computer system validation. Linkage of these workstreams is important to establish one general data integrity concept e.g. creation of data maps, detection of GAPs, evaluation of risk assessments and finally dealing with high-risk GAPs. The internal communication about GAPs arose in different workstreams and facilities is meaningful to find the right CAPA-Actions. Most important is the integration of an open culture of data integrity. Experts can help to integrate this culture into the company during talking to staff and interviewing operators about their work. Everyone must feel their own responsibility for product quality and patient health and data integrity compliance can be reached easily.


Author: Dr. Anna-Lena Hürter, Life Science Consultant


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