Understanding GxP Compliance in the Lab

New standards are evolving in the digital era with compliance in the laboratory. New means of data tracking are leading to higher standards of robust recordkeeping. In the digital age of permanent and instantaneous recordkeeping, it is more important than ever to structure your business around the maintenance of good records within your FDA audit trail, or risk being fined, audited, or other potentially disastrous consequences. Proper management of your audit trail can lead to a streamlined process, accurate and instantaneous analytics of every step of the process, and a much easier long-term storage solution than paper records.

Data integrity and GxP compliance are two very important terms for manufacturers and scientists who are trying to achieve the best for their customers, as well as their facilities.

GxP compliance is an overarching term covering a broad range of regulations related to the life sciences industries, such as the fields of food and medical products. GxP encompasses multiple compliance-related activities such as good laboratory practices (GLP), good document practices (GDP), good manufacturing practices (GMP), and good clinical practices (GCP). These requirements are practiced to ensure the integrity of data and that correct steps are taken for public safety. 

It is very important that these compliance requirements are implemented based on the type of the product and the country where the products are being sold. The FDA defines an audit trail as, “a secure, computer-generated, time-stamped electronic record that allows for the reconstruction of the course of events relating to the creation, modification, or deletion of an electronic record.” In short, “an audit trail is a chronology of the ‘who, what, when, and why’ of a record.” 

The cost of non-compliance

The FDA has a right to review and copy all records, physical and electronic. All individuals responsible for errors or non-compliance can be removed from their positions within the GxP chain. Facilities that are found to be in violation of GLP compliance can be issued warning letters and business can be halted until GLP standards are achieved again. The damage done to your business can be irreversible. Business relations will fall apart as deadlines cannot be fulfilled. Research and production time will be lost until compliance can be proven. The necessary re-establishment of trustworthiness in the market will also be necessary; however, this is often impossible. Internally, the cost of not following GxP can manifest in varied ways. One of which is employee time lost to redoing trials, either for inaccurate results, misrepresentative results, or incomplete data. Misinterpreting analysis from flawed data sets can result in time and monetary loss into investigation dead ends. The key to GxP is strong data integrity. The FDA explains, “data integrity refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate.” 

Backup data, as well as metadata, must be included in the complete records. Backup data pertains to “exact and complete” records of “complete data derived from all tests,” which are secured to prevent alteration, deterioration, or loss. Metadata is defined as, “contextual information required to understand data.” As a number is meaningless without units, metadata is any correlating information between datasets and results. Some examples are the mass units of an individual measurement, the date and timestamp, name of the recordkeeping employee, instrument ID number, lot or batch number, and any other information useful in maintaining audit trails. 

In 2018, the FDA revised guidelines to update their focus on data integrity with the top priority being monitoring the increasingly complex supply chains of modern pharmaceuticals. The integration of digital systems into the processes of manufacturing and testing has allowed for more robust data integrity recording, reporting, and preservation.

Here are key tips to ensure your lab is following the most recent FDA guidelines:

Know your audit trail. Establish new protocols with the audit trail as the core of your documentation process, including establishing new SOPs that include streamlined protocols for data integrity and electronic records within your audit trail. Create a new digital system with in-built static record capture and complete GxP record metadata that allows for a more streamlined process. These new regulations can help build good recordkeeping practices internally and offer easier business workflow. Train all employees on the importance of GxP and good record-keeping practices. Correct data can only improve your company’s efficiency and interdepartmental communication. Don’t fight digital reorganization; embrace all of the ways it can save time and effort. Use digital signatures to maintain records—electronic copies are acceptable as true copies. Create a digital recordkeeping process that is compliant with GxP measures. Implement and follow it diligently, with frequent internal audits to maintain consistency.

Validate your digital workflow. Create an accurate log that is reproducible from instrument readings, with consistent metadata, for all processes. All electronic data should be immediately compiled into your GxP workflow. There shouldn’t be any extra pieces of paper collecting data before it is compiled into a complete and validated record. All data must be included in the GxP record and can only be excluded if a written valid scientific justification is given. All records should be instantaneously recorded in such a way that they prevent future modification.

The FDA recommends “audit trails subject to regular review should include, but are not limited to, the following: the change history of finished product test results, changes to sample run sequences, changes to sample identification, and changes to critical process parameters.” This means you should always be reviewing your workflow for inaccuracies due to machine or human error, and simplifying processes for recording and capturing data in such a way that it is permanently recorded and immediately accessible. “FDA requires complete data in laboratory records, which includes raw data, graphs, charts, and spectra from laboratory instruments (§§ 211.194(a) and 212.60(g)(3)).” Although paper records are still acceptable for many recording instruments, many instrument files produce data that cannot be accurately represented in a printable form in a way that will satisfy the requirements as a true copy, so changing over into digital systems will only save you time later on and remove your requirement for years of physical records storage.

The benefits of quality GxP in the lab

Good digital GxP can result in the live monitoring of processes, labor, and results. This data can be infinitely useful in business analytics used to expand your business, hire new employees, and meet future demands. Complete implementation of GxP will include both a computer system, such as a laboratory information management system (LIMS) or an electronic batch record (EBR) designed to save data immediately after entry, combined with laboratory standard operating procedures inclusive of entering data into the electronic system immediately after collection. 

The FDA also specifically prohibits testing into compliance which is defined as, “sampling and testing with the goal of achieving a specific result or to overcome an unacceptable result (e.g., testing different samples until the desired passing result is obtained).” Any known or even suspected falsification or alliteration of any record in the audit trail is cause for immediate audit by the FDA. It is also specifically prohibited to attempt to internally resolve any know compliance issue without alerting the FDA.

Make sure you establish and follow good laboratory practices, because if you discover an error in your system after a compliance issue arises, you are literally going to be asking for an audit.