483 Roundup: Four Device Firms Cited for GMP, Other Failures

March 15, 2019

The FDA hit four facilities for various failures including inadequate validations, CAPAs, written procedures and supplier evaluations.

Datascope: Failure to establish validation procedures or to conduct risk analysis for its Cardiosave hybrid intra-aortic balloon pumps landed Datascope a nine-item Form 483 following a July 30 to Oct. 3, 2018 FDA inspection of its Maywah, New Jersey facility.

Numerous test protocols, including for software design validation and risk management processes were found to be lacking, inspectors said. For example, severity ratings were inconsistent with those identified in a hazard analysis and risk management report. In addition, none of the battery packs for the aortic balloon pump passed acceptance criteria.

A design change procedure failed to identify new or altered risks or hazards or the potential failure of the device to address fluid ingress after modifications were made. The agency inspector found that there “was no design plan documentation” for numerous design changes.

The FDA said the firm’s design verification didn’t confirm that design output met design input requirements. For example, design verification of the performance testing was conducted in 2011, but no verification was performed for software updates since 2011 despite several software updates.

Datascope also failed to document corrective and preventive actions or statistical analyses of failures. Investigators noted that procedures for rework of nonconforming product was not adequately established. In addition, suppliers were not properly vetted o confirm they could meet specifications.

Nurses Assist: Failure to identify actions needed to correct and prevent microbial contamination landed Nurses Assist an FDA Form 483 following an Oct. 15 to Oct. 25, 2018 inspection of the firm’s Haltom City, Texas facility.

The maker of senior care products for institutions initiated and closed at least 32 nonconformances due to bioburden issues since July 2017, but it didn’t establish procedures to confirm that corrective actions were effective.

For example, the manufacturer failed to validate the effect of a sterilization process for sterile water and saline bottles that are packaged in tracheostomy care kits.

The agency cited the firm for failure to establish procedures to prevent contamination by substances that may have an adverse effect on product quality. Specifically, inspectors observed a leaking filter in a system used for manufacturing USP sterile water and saline, as well as a rusty metal support above the saline mixing tanks that were not closed properly.

Wellman Advanced Materials: Written procedures were found to be missing for a range of quality parameters at Wellman Advanced Materials’ Johnsonville, SC, plant during a Dec. 10-13, 2018 FDA inspection.

The compounder of thermoplastic resins lacked written procedures for the quality control unit or records of annual evaluations or reviews for FDA-regulated products.

Records indicated that GMP training had not been conducted since 2014 and training for laboratory personnel was not documented.

“GMP training is not conducted on a continuing basis and with sufficient frequency to assure that employees remain familiar with GMP requirements,” the agency said.

Belluscura: The FDA hit Plano, Texas devicemaker Belluscura with a Form 483 for failing to properly document evaluations of potential suppliers to ensure that their products conformed to specified requirements.

In a Nov. 19-29, 2018 inspection, the agency noted that the facility evaluated prospective suppliers using a questionnaire prior to an audit but had failed to do that for two of its suppliers.

Read the Datascope Form 483 here: www.fdanews.com/03-12-19-datascopecorp483.pdf.

Read the Nurses Assist Form 483 here: www.fdanews.com/03-12-19-nurseassistllc483.pdf.

Read the Wellman Advanced Materials Form 483 here: www.fdanews.com/03-12-19-wellmanadvancedmaterialsllc483.pdf.

Read the Belluscura Form 483 here: www.fdanews.com/03-12-19-belluscurallc483.pdf.

Ten Inspection Objectives

When examining CAPA systems, FDA investigators focus on 10 specific areas:

  1. Compliance with the Quality System Regulation (QSR);
  2. Sources used to identify problems;
  3. Examination of unfavorable trends;
  4. Quality of the data information system:
  5. Statistical methods;
  6. Failure investigations;
  7. Corrective action;
  8. Evaluation of corrective action’s effectiveness;
  9. Verification that corrective and preventive actions were implemented and documented; and
  10. Dissemination and management review of CAPA results.

Investigators will check to see if a manufacturer has an understanding of the terms and concepts involved in CAPA management, such as nonconformances, quality audit, corrective action and preventive action. So CAPA procedures must include definitions of these and other terms. The FDA doesn’t specify what definitions to use.

Quality systems expert Dan O’Leary, president of Ombu Enterprises, recommends looking to the QSR and international standards such as ISO 8402:1994, ISO 9000:2005 or ISO 9000:2015 to develop definitions, but be sure to cite the source in each case.

FDA investigators will check the kind of data collection and monitoring a devicemaker conducts as part of efforts to catch trouble when, or even before, it occurs. The sources a company uses to identify nonconformities should include data and information collected during manufacturing, such as acceptance activities, and after distribution, such as complaint, service and returned product records. Quality audits, installation reports and litigation records also are acceptable sources.

Devicemakers should also examine their historical records, such as component test results, for shifts or trends that could predict a potential nonconformance. Investigators want to see evidence that such trends were studied and appropriate preventive actions considered.

The primary complaint in FDA warning letters featuring CAPA citations is that, although the devicemaker had established CAPA procedures, it did not follow or document them properly.

Excerpted from the FDAnews management report: Creating QSR-Compliant CAPA Systems: A Practical Guide for Devicemakers.