Drug GMP violations lead plasma 483 items.Violations of drug Good Manufacturing Practice Good Manufacturing Practice or GMP (also referred to as 'cGMP' or 'current Good Manufacturing Practice') is a term that is recognized worldwide for the control and management of manufacturing and quality control testing of foods and pharmaceutical products. (GMP GMP (guanosine monophosphate): see guanine. ) rules (21 CFR CFR
See: Cost and Freight 211) continue to lead 483 citations to plasma derivative companies, FDA FDA
Food and Drug Administration
n.pr See Food and Drug Administration.
n.pr the abbreviation for the Food and Drug Administration. statistics show.
Susan Frantz-Bohn, a member of the Center for Biologics inspection task force, told a Feb. 24 Cambridge Healthtech conference on blood screening in McLean, VA, that "211 continues to be a major topic" in 483s for fractionators, as well as blood banks and plasma-collection centers.
She listed the following 10 violations, in order of prevalence, on 483s of 30 fractionators inspected in fiscal 1997 and fiscal 1998 to date:
1. Quality control/quality assurance. Lack of failure investigation, lack of documentation, incomplete corrective action A corrective action is a change implemented to address a weakness identified in a management system. Normally corrective actions are instigated in response to a customer complaint, abnormal levels if internal nonconformity, nonconformities identified during an internal audit or investigation, lack of annual reviews and evaluations of batch records.
2. Lack of process validation and cleaning validation The introduction to this article provides insufficient context for those unfamiliar with the subject matter.
Please help [ improve the introduction] to meet Wikipedia's layout standards. You can discuss the issue on the talk page. .
3. Failure to establish and follow standard operating procedures standard operating procedure Medtalk A technique, method or therapy performed 'by the book,' using a standard protocol meeting internally or externally defined criteria; a formal, written procedure that describes how specific lab operations are to be performed. (SOPs) to prevent microbial microbial
pertaining to or emanating from a microbe.
the breakdown of organic material, especially feedstuffs, by microbial organisms. contamination limits in media fills. Frantz-Bohn said FDA is concerned about filling conditions not "mimicking actual conditions because employees go on lunch breaks, or things go wrong."
4. Inadequate environmental monitoring, where monitoring is not done in actual use conditions
5. Lab controls, establishing controls with appropriate specifications. An example is a lack of data to support operating parameters for lyophilizers and pasteurizers, such as dry-heat ovens.
6. Incomplete training records. Frantz-Bohn said it was "common to find incomplete training SOPs, especially with virtual inspections and media fills."
7. Failure to establish cleaning procedures in aseptic processing.
8. Lack of SOPs for production process controls. Frantz-Bohn commented: "This is commonly cited and I thought it would be lower [on the list], but there are still processes where FDA investigators don't have the procedures. It's something that's so basic."
9. Failure to calibrate To adjust or bring into balance. Scanners, CRTs and similar peripherals may require periodic adjustment. Unlike digital devices, the electronic components within these analog devices may change from their original specification. See color calibration and tweak. instruments and electronic equipment.
10. Viral inactivation inactivation /in·ac·ti·va·tion/ (in-ak?ti-va´shun) the destruction of biological activity, as of a virus, by the action of heat or other agent. . Inspections found discrepancies with viral inactivation data compared with SOPs, she said. "There were some cases where parameters were different in SOPs than how the validation of viral inactivations were done," Frantz-Bohn added. She said some SOPs were being conducted with invalidated parameters, while some involved temperature faults.
Frantz-Bohn said warning letters resulted from some of the 30 audits, but not all.
Dr. Thomas Lynch, Ph.D., senior staff fellow in the Division of Hematology, Office of Blood Research and Review, said in an interview that the agency - probably this month - will issue an addendum to its plasma compliance program regarding viral validation. He said the addendum becomes effective automatically. (See Next Page)
Lynch also said that how to handle out-of-specification results continues to be a problem for fractionators, "not in terms of designing SOPs, but following them." Due to the 1993 "Barr decision" on out-of-spec results, Lynch said: "A lot of SOPs seem to have been drafted by lawyers, which is why laboratories can't follow them."
Lynch said FDA will likely not issue guidance on out-of-spec results - which would require the concurrence CONCURRENCE, French law. The equality of rights, or privilege which several persons-have over the same thing; as, for example, the right which two judgment creditors, Whose judgments were rendered at the same time, have to be paid out of the proceeds of real estate bound by them. Dict. de Jur. h.t. of other product review centers - until the new drug GMPs become final. He added that guidance can be culled from the May 1996 proposed GMPs, but it is not binding.
FDA began enforcing the drug GMPs on the blood industry around 1991, said Eva Quinley, a trainer for Ortho Diagnostics. She told a Ortho-American Blood Resources Assn. training seminar in Herndon, VA, March 3, that because of FDA's inspection crackdown, plasma firms would be wise to organize quality assurance/quality control units that report to top management, rather than to the operations unit. She said this will minimize bias when conducting internal audits.
A former blood bank regulatory affairs/ quality assurance executive, Quinley also advised the adoption of an ISO (1) See ISO speed.
(2) (International Organization for Standardization, Geneva, Switzerland, www.iso.ch) An organization that sets international standards, founded in 1946. The U.S. member body is ANSI. 9000-style Total Quality Assurance System, which is centered on customer requirements, including FDA as a "customer."
Quinley said error management also will "give you the biggest bang for the buck in GMPs, by capturing errors and complaints and ensure corrective action is taken." She noted that inspec-tors are increasingly looking at error and accident reports during audits - in much same way inspec-tors of device firms go straight for the complaint file before doing anything else.
A special package containing plasma inspection guides addressing FDA and foreign audits, plus other important guidance, is available for a special rate of $30 plus retrieval. Doc. 108324M.