FDA Concerned with Repeat Inspectional Findings
FDA continues to be concerned with the same top inspectional findings repeating every year during drug and device inspections, CDER Office of Product Quality acting branch chief Andrea Chamblee told the Food and Drug Law Institute’s annual meeting in Washington, DC 5/12. For example, the top inspectional findings for both drugs and devices were related to inadequate procedures, she said. [see top 10 findings for drugs and devices below]
There are plenty of Warning Letters citing the top inspectional violations, Chamblee said, adding that “these repeat violations happen so often, the investigators are going to look for it. It is something they are not going to skip over because they know they are recurring problems.”
Firms should be performing better internal audits, according to Chamblee, and it is disturbing that some firms are not auditing themselves, or not doing anything with the audits they conduct, or not reporting audit results to management and not acting on problems discovered. In my experience, there are some company cultures that seem to think it is a good sign to have nothing found on an audit.
Former FDAer and now-consultant at QualityHub Tim Wells echoed the need for good internal audits. “It is amazing how prevalent FDA findings are centered on the lack of internal audits,” he said. “Don’t use an FDA inspection as an internal audit or as a barometer of your compliance to any GMP requirement.”
Wells told FDLI that there is a “false sense of security” with firms after they receive an inspection and a Form 483 with few findings listed. Executive leadership does not understand that an FDA inspection is just a snapshot. He said inspections are shorter and investigators are not digging as deep due to resource constraints. “Just because the agency hasn’t found it doesn’t mean you are good to go,” he said. “That is why pharma, devices and biologic companies must have internal audits. It’s Amazing how prevalent FDA findings are in lack of internal audits.”
Additionally, Wells said he is seeing evidence of ISO audits that are stronger than FDA inspections in some cases. Because of the global economy, he said the agency now appears to be doing a “reboot” to better focus their investigators so that they are better qualified and more in line with ISO.
Mayer Brown partner Mark Mansour told the conference that it appears FDA is more aggressive with its enforcement over the past year, and already through April there have been over 200 Warning Letters issued. “From my perspective, enforcement is going to get tougher,” he said. “There is always the question of what happens if a Republican president is elected. I have found except for large policy issues, that does not really cause a whole lot of change. The people there are going to continue to do their jobs as they were trained.” A lot of the people that have been hired under the Clinton and Obama administrations are enforcement-minded, Mansour noted, adding that many are not going anywhere after the election as they seem to be more career-oriented than previous agency employees.
TOP DRUG INSPECTIONAL OBSERVATIONS 2015
21 CFR 211.22(d) The responsibilities and procedures applicable to the quality control unit are not in writing or fully followed.
21 CFR 211.160(b) Laboratory controls do not include the establishment of scientifically sound and appropriate specifications, standards, sampling plans or test procedures.
21 CFR 211.192 There is a failure to thoroughly review any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications.
21 CFR 211.113(b) Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written or followed.
21 CFR 211.100(a) There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess.
21 CFR 211.42(c)(10)(iv) Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.
21 CFR 211.165(a) Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications or identity and strength of each active ingredient prior to release.
21 CFR 211.110(a) Control procedures are not established which monitor the output or validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.
21 CFR 211.67(a) Equipment and utensils are not cleaned, maintained or sanitized at appropriate intervals to prevent malfunctions or contamination.
21 CFR 211.68(a) Routine calibration or inspection of equipment is not performed according to a written program designed to assure proper performance.
TOP DEVICE INSPECTIONAL OBSERVATIONS 2015
21 CFR 820.100(a) Procedures for corrective and preventive action have not been adequately established.
21 CFR 820.198(a) procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been adequately established.
21 CFR 820.50 Procedures to ensure that all purchased or otherwise received product and services conform to specified requirements have not been adequately established.
21 CFR 820.75(a) A process whose results cannot be fully verified by subsequent inspection and test has not been adequately validated according to established procedures.
21 CFR 803.17 Written MDR procedures have not been developed, maintained or implemented.
21 CFR 820.90(a) Procedures have not been adequately established to control product that does not conform to specified requirements.
21 CFR 820.100(b) Corrective and preventive action activities and/or results have not been [adequately] documented.
21 CFR 820.22 Procedures for quality audits have not been adequately established.
21 CFR 820.30(i) Procedures for design change have not been adequately established.
21 CFR 820.181 A device master record has not been adequately maintained.