Data Integrity Violations detected by the FDA at US Company

In June, the U.S. FDA issued a Warning Letter to SC Johnson Professional, Inc. (formerly Deb USA, Inc.), an U.S. American drug manufacturing facility.

According to the FDA Warning Letter, the firm failed to establish adequate written responsibilities and procedures applicable to the QC unit, laboratory controls that include appropriate specifications, standards and test procedures and required laboratory control mechanism. In addition, the U.S. FDA mentioned that the company missed to ensure that laboratory records included complete data derived from all necessary tests and to conduct appropriate laboratory testing required to be free of objectionable microorganisms.

For the FDA, it is important to underline that additionally the inspected firm does not adequately ensure the accuracy and integrity of data to support the effectiveness, safety and quality of the drugs manufactured.

According to the Warning Letter, the U.S. FDA reviewed the response sent by the firm on November 20th, 2018.

FDA expectations - Data Integrity

In relation to the Data Integrity violations, the U.S. FDA now expects a Data Integrity remediation. Some of their expectations are listed below:

• A comprehensive investigation into the extent of the inaccuracies in data records and reporting. The investigation should include:
  
  1) A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations and systems to be covered by the assessment; and a justification for any part of their operation that they propose to exclude.
  
  2) Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. The U.S. FDA recommends that these interviews are conducted by a qualified third party.
  
  3) An assessment of the extent of data integrity deficiencies at the facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility's operations in which you discovered data integrity lapses.
  
  4) A comprehensive retrospective evaluation of the nature of the testing data integrity deficiencies. The U.S. FDA recommends that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.
   
• A current risk assessment of the potential effects of the observed failures on the quality of their drugs. Their assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.
  
• A management strategy for the firm that includes the details of their global CAPA plan. Their strategy should include:
  
  1) A detailed corrective action plan that describes how they intend to ensure the reliability and completeness of all the data they generate including analytical data, manufacturing records, and all data submitted to FDA.
  
  2) A comprehensive description of the root causes of their data integrity lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. They should indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data in their firm.
  
  3) Interim measures describing the actions they have taken or will take to protect patients and to ensure the quality of their drugs, such as notifying their customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.
  
  4) Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of the company's data.
  
  5) A status report for any of the above activities already underway or completed.

FDA expectations - Quality Unit

In addition, the U.S. FDA mentions several further expectations, which are mostly related to Quality Unit topics.
Some of these expectations are listed below:

• A comprehensive assessment and CAPA to ensure the Quality Unit is given the authority and resources to effectively function. The assessment should include, but not be limited to:
  
  1) An evaluation of each procedure used by the firm to ensure they are appropriate, sufficient, and robust.
  
  2) Provisions for QU oversight throughout their operations to evaluate adherence to appropriate practices.
  
  3) A complete and final review of each batch and its related information before the QU disposition decision.
  
  4) Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.
  
• An independent assessment and report of all chromatographic data associated with released drug products within expiry to determine if each was performed appropriately.
  
• A full assessment of their practices. Based on this assessment, the firm shall provide procedures that clearly define the circumstances, and associated scientific justification.
  
• An investigation into the failure of their laboratory personnel to follow written procedures.
  
• A comprehensive, independent review of their chemical and microbiological laboratory practices, procedures, methods, equipment, and analyst competencies. Based on this review, the firm should provide a detailed CAPA plan to remediate their laboratory system. The plan should include the process they will use to evaluate the effectiveness of the implemented CAPA plan.
  
• The plan should have an independent qualified laboratory perform chemical and microbiological testing of each of their drug products within expiry to ensure they possess all of their required quality attributes. The firm should provide the third-party test methods and test results. If testing any previously released batch yields any OOS results, they should indicate the corrective actions they will take, including notifying customers and initiating recalls.
  
• Procedures and arrangements with third parties associated with release and distribution of their drug products.
  
• An explanation for why full quality control testing of lots released without documentation of full testing will not be completed. Identify actions taken to ensure these products are not further distributed until microbiological testing is complete.
  
• A fully remediated procedure for their batch disposition process and a description of the changes made to the procedure.

The FDA strongly recommends engaging a GMP consultant to rectify the deficiencies.

For further details please see the FDA's Warning Letter to Deb USA.