Today more than ever, Data Integrity has become a significant factor in being a compliant manufacture of pharmaceutical/life sciences products. Many regulatory agencies are taking a hard look at operations because of irregularities to have been unearthed during cGMP inspections and PreApproval Inspections (PAI’s).
Why is this so important? Several reasons:
1. It undermines the safety/efficacy and assurance of quality that consumers have when they take these products
2. It breaks trust that the products meet specifications and have been manufactured in accordance with approved procedures
3. We’re relying on manufacturers to perform within the law and the agreements that are part of their license to produce and distribute regulated products.
So where are the problems being seen and what type of examples highlight the dangers of not assuring that data integrity does not occur?
Sadly, frequently seen examples include:
1. Backdating entries.
2. Fabricating data.
3. Copying existing data as new data.
4. Rerunning samples without a credible strategy.
5. Discarding data that might not be at specification.
6. Releasing failed product.
7. Testing into compliance by testing until specifications are met.
8. Not saving electronic data, overwriting said data or discarding hard copy data.
In performing routine audits, there are several potential red flags that often alert inspectors to the potential of Data Integrity issues. Some of these include:
1. In circumstances where employees sign for completing batch steps but were not even on-site when the activities were performed.
2. Testing, including stability samples, that were tested late but signed off as being analyzed on time.
3. Data generated for samples that never existed.
4. Chromatograms used for releasing a batch that were generated from a passing batch and applied to a failing batch.
5. Chromatograms generated for an innovator drug standard being used to pass batches of a generic alternative.
6. Test method validation data being generated for a test method and then applied against an entirely different test method.
7. Microbiological sterility testing being passed in cases where growth was observed.
8. Release of products containing known contaminants.
9. Rewriting of the laboratory records to produce positive results.
10.Making up records during an FDA inspection.
What does all this mean for your company if you don’t have an effective policy/procedure for assuring that Data Integrity is not occurring? The consequences are serious and can include the following:
1. A recall of the company’s products.
2. The potential for a Warning Letter.
3. Almost certainly an import alert for foreign companies.
4. A legal injunction to sell and market the products.
5. Seizure of products in Interstate Commerce and at the company’s own premises
6. Application Integrity Policy invocation (AIP); this means that all pending applications are halted, possible withdrawal of pending affected applications, and no further action to approve products until remediation action is taken.
If Data Integrity is discovered, is recommended that a pharmaceutical consultant is hired to assist in the rebuilding of the company’s trust with the regulatory agency. This is done by including the following actions:
1. Third-party auditing the work that is affected.
2. Understanding the scope of the problem that these be resolved.
3. Building a credible CAPA program.
4. Removing individuals that had management and line responsibilities for the issues discovered.
5. Performing a verification audit to assure resolution of the problem once corrective actions have been concluded.
6. Post approval, build and put a continuous improvement program in place so that the culture of the organization moves away from this type of practice in order to assure that the new resolutions are sustainable.