GMP

Data Integrity Issues & Concerns

Good evening everyone………..

Today we are going to discuss on Data integrity issues

What is Data Integrity?

  • Complete, consistent, and accurate data to assure patient safety and product quality.
  • Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded,original or a ‘true copy’, and accurate (ALCOA).
  • Good Documentation Practices for Static and Dynamic Records.
  • Data integrity should be maintained throughout the data life cycle, including, but not limited to data creation, processing, archiving and disposition after record’s retention period

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What is ALCOA?

  • Attributable – Traceable to a unique individual
  • Legible – Data must be recorded permanently and be readable
  • Contemporaneously – Activities must be recorded at the time they occur
  • Original or a true copy – first capture of data (not transcribed
    data), must review the original record, must retain the original or certified copy of the original record.
  • Accurate – records must be accurate, which is achieved thru the Quality Management System

What are the Regulations?

  • Data in accordance with cGMP requirements for drugs (i.e., as required by 21 CFR parts 210, 211,and 212).
  • Part 210 – Current Good Manufacturing Practice in Manufacturing,Processing,
  • Packing, or Holding of Drugs; General.
  • Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals.
  • Part 212 – Current Good Manufacturing Practice for Positron Emission Tomography Drugs.
  • Q7A – Active Pharmaceutical Ingredients.

Regulations – Data Integrity : Requirements with respect to data integrity in parts 211 and 212 continued:

  • 211.188, 211.194, and 212.60(g) (requires “complete information,” “complete data derived from all tests,” “complete record of all data,” “original records have been reviewed for accuracy, completeness, and compliance with established standards,” and “complete records of all tests performed”).
  • 211.192 (requires production and control records be “reviewed”) 211.101(c) and (d), 211.103, 211.182, 211.186(a), 211.188(b)(11), and 211.194(a)(8) require records be “reviewed” by a second person.

Why is Data Integrity Important?

  • FDA cGMP inspection(s) have uncovered violations with data integrity issues.
  • Data integrity is an important component of industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA’s ability to protect the public health.
  • Data integrity-related cGMP violations may lead to regulatory actions, including warning letters, import alerts, and consent decrees.
  • The underlying premise in 210.1 and 212.2 is that cGMPs sets forth minimum requirements to assure drugs meet standards of the Federal Food, Drug, and Cosmetic Act (FD&C Act) regarding safety, identity, strength, quality, and
    purity.
  • FDA’s authority for cGMP comes from FD&C Act section 501(a)(2)(B).
  • 501(a)(2)(B) states: a drug shall be deemed adulterated if “the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirement of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.”
  • Reliability on the information used to ensure the quality of the drugs that
    consumers will take
  • Data integrity problems break trust
  • FDA rely on firm’s to do the right thing when FDA is not present.

Examples of significant issues

  • No raw data to support records
  • Creating inaccurate and incomplete records
  • Test results for one batch used to release other batches
  • Backdating
  • Fabricating data
  • Discarding data
  • Repeated tests, trial runs, sample runs (testing into compliance)
  • Changing integration parameters of chromatographic data to obtain passing results
  • Deletion/manipulation of electronic records
  • Turning off audit trail
  • Sharing password
  • Inadequate controls for access privileges
  • Inadequate/incomplete computer validation
  • Inadequate investigations
  • Inaccurate reporting of microbial, sterility, or endotoxin data results
  • Loss of data during changes to the system
  • Activities not recorded contemporaneously
  • Employees that sign that they completed manufacturing steps when the employees were not on premises at the time the steps were completed.

Things to consider…

  • Is data integrity a problem at your facility? What measures are in place to prevent data integrity problems?
  • Are internal audit procedures adequate? What measures are in place and will they detect data integrity issues?
  • Does senior management cultivate adequate and accurate reporting of events when things go wrong during manufacturing…during testing?
  • Train personnel to detect and prevent data integrity as part of routine cGMP training.

Where does the Agency find Data Integrity Issues?

  • Domestic and international facilities
  • Small and large pharmaceuticals companies
  • Manufacturing operations
  • Quality units, including quality control laboratories (chemistry and microbiology)
  • Clinical Trials

Things to consider…

  • Existing systems should be able to ensure data integrity, traceability and reliability
  • Firms who outsource operations should have robust systems in place to verify and compare data generated by the contractor

Conclusion

  • Once data integrity issues are found during an inspection, a change to a written
    procedure or firing an employee is not enough
  • Quality Risk Management approaches to prevent, detect and control potential risk
    are essential

FDA recommends that data integrity problems identified during inspections
be addressed?

  • The firm should demonstrate effective remediation. For example, By:
  • Hire a third party auditor
  • Determine the extent/scope of the problem
  • Implement a global corrective action plan
  • Removing individuals responsible for problems from cGMP positions

References

  • Part 210 – Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General.
  • Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals.
  • Part 212 – Current Good Manufacturing Practice for Positron Emission Tomography Drugs.
  • Q7A – Active Pharmaceutical Ingredients.

                                                                          Thank you………..

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