-The SOP-GMP or sometimes referred to as Standard Operating Practices (SOP's) are used to lay out operations consistently and repeatedly in the same repetitive manner. SOP’s must be available for every task that is used in the manufacture or testing of a regulated product. SOP’s ensure that all processes and standard operation procedure are consistently replicated, so even when there are changes in personnel, organizations avoid inconsistencies and do not run unnecessary safety risks.
Standard Operating Procedures or SOP's are written step-by-step procedure that quality control (QC), quality assurance (QA), and production units use in order to assure that the accuracy and precision of the original product development is maintained in the transformation from small trial and batch work to full scale production of the product. SOP-GMP is an essential part of the consistent replication of the tasks that are used to produce a regulated product to a pre-approved quality specification.
Standard Operating Procedures are active documents that are routinely reviewed and amended as production processes are repaired, altered or replaced. detail written instructions describing specific steps to follow in all activities under defined conditions, they are used to accomplish standardization when performing specific functions and used to ensure approved methodologies are used wherever possible. Having defined all the appropriate standard operating procedures and practices they are then used as audit standards to ensure that these define methods are being meticulously followed and adhered to.
It can be deduced from what is written above that standard operating procedures forms the backbone of regulatory compliance activities in all companies regulated by Good Manufacturing Practices (GMP) rules and regulations.
Having described the use and importance ascribed to Standard Operating Procedures it is incongruous to now inform you that the number one failure in compliance is; “not following written instructions”. This is closely followed by the number two failure: “no documented instructions available”.
It is hard for any validation professional to understand the mentality of persons that would patiently wait for a regulatory visitation – knowing it was routine for their operators and laboratory technicians to execute tasks without using a documented standard operating practice document.
It therefore becomes pretty obvious and very essential for personnel to be trained in the use of documented "standard operating practice" documents in the execution of their daily tasks. Thus demonstrating that they are aware of why and how these SOP-GMP activities play such an important role in fulfilling the specific company’s regulatory requirements from WHO, FDA, EMEA or other national health authorities. Health authorities world-wide expect pharmaceutical, cosmetic and food producers to use approved manufacturing processes in written SOP-GMP format.
1. Failure of management with executive
responsibility to review the
suitability and effectiveness of the quality system at defined intervals
and with sufficient frequency according to established standard operating procedures to
ensure that the quality system satisfies the requirements of Part 820
and the manufacturer's
established quality policy and objectives, as required by 21 CFR
Specifically, there is no evidence that SOP-GMP related management reviews have been
2. Failure to establish procedure for, and to conduct, quality
assure that your firm's quality system is in compliance with the
quality system requirements, and to determine the effectiveness of the
system, as required by 21 CFR 820.22. Specifically, there is no evidence
that you have established quality audit standard operating procedures or that quality
audits have been performed.
3. Failure to ensure that personnel are adequately trained to perform their assigned functions and to document training, as required by 21 CFR 820.25(b). Specifically, employees involved in the manufacturing, packaging, testing, shipping, and complaint handling of in vitro reagents have not been trained in current Good Manufacturing Practice or the use of standard operating procedures; i.e. SOP-GMP. It was noted; you were able to provide documentation of any type of training for only one of your current employees.
4. Failure to establish and follow document approval, distribution
procedure, as required by 21 CFR 820.40. For example, standard operating procedures on how
control approval, distribution, and changes to device master records
specifications, device history records (DHRs) and labeling for your
strep A and hCG in vitro diagnostics were not available and documents
not signed as approved for use were being used in product manufacturing
and finished product testing locations during this inspection.
5. Failure to establish standard operating procedures to ensure that all purchased or
otherwise received product and services conform to specified
requirements, as required by 21 CFR 820.50. For example, quality
requirements to be met by your contract
manufacturer of your strep A and hCG in vitro diagnostics have not been
defined or documented.
Failure to develop,
conduct, control, and monitor production processes to ensure that your
conform to their specifications, as required by 21 CFR 820.70. For
do not have any cleaning standard operating procedures for the equipment used
in the production of strep A and hCG in vitro diagnostics.
7. Failure to ensure that all inspection, measuring, and test
equipment, including mechanical, automated, or electronic inspection and
test equipment, are suitable for their intended purposes and are capable of
producing valid results, as
required by 21 CFR 820.72 (a). Your firm has no approved standard operating procedures to ensure
that equipment is routinely calibrated, inspected, checked and
maintained. For example, procedures for calibration, inspection, checks
and maintenance of your firm's digital scales, autoclave and
spectrophotometer used in the manufacture
and testing of your strep A and hCG in vitro diagnostics were not
8. Failure to validate with a high degree of assurance and approve according to established standard operating procedures a process whose results cannot be fully verified by subsequent inspection and test, and failure to document such validation activities and results, as required by 21 CFR 820.75(a). For example, there is no standard operating procedures in place for validation of your firm's manufacturing process, cleaning operations, software calculations or filling operations for your strep A and hCG in vitro diagnostics.
9. Failure to use a documented standard operating procedures for incoming product inspection and acceptance purposes, as required by 21 CFR 820.80(b). For example, there is no documentation of acceptance activities for incoming reagents, reagent bottles, bottle droppers, bottle caps, or labeling for your strep A and hCG in vitro diagnostics.
10. Failure to establish and maintain standard operating procedures for finished device
acceptance to ensure that each production run, lot, or batch of finished
devices meets acceptance criteria, and to hold finished devices in
quarantine until all activities required by the DMR are completed, as
required by 21 CFR 820.80(d).
Specifically, entire lots of your strep A and hCG in vitro diagnostics
tested and released after the first day of assembly/production before
activities required in the DMR had been completed. For example, the
lots were released prior to completion of all activities required in the
Mainline Confirms Strep A, lot 94610; Mainline confirms DOTS Strep A,
Mainline confirms III hCG serum/urine, lot 96380 and Mainline Maxie
test urine hCG, lot 418F30.
11. Failure to establish and maintain standard operating procedures for implementing
corrective and preventive action, as required by 21 CFR 820.100.
Specifically, no corrective and preventive action procedures were
available during this inspection.
12. Failure to establish and maintain SOP-GMP procedures to control labeling activities to assure that a designated individual has examined labeling for accuracy including, where applicable, the correct expiration date, control number, storage instructions, handling instructions, and any additional processing instructions prior to labeling release for storage or use, as required by 21 CFR 820.120(b). For example, the DHR does not include a date or signature of a person who examined and approved the expiration date and lot numbers on your labels for your Strep A and hCG in vitro diagnostics.
13. Failure to use documented standard operating procedures for verification of the label and labeling used for each
production lot in the device history record, as required by 21 CFR
820.120(d). For example, the lot code and expiration labeling for the
Strep A and hCG pregnancy screening test kits are not recorded in the
14. Failure to maintain DMRs that include, or refer to the location of, device specifications, as required by 21 CFR 820.181(a). For example, the DMRs for your strep A and hCG in vitro diagnostics do not include or refer to the locations of all specifications for all reagents, bottles, dropper tip caps or dropper tips.
15. A serious SOP-GMP failure in not establishing or maintaining a design history file (DHF) for each type of device, as required by 21 CFR 820.30(j). For example, you have failed to provide a DHF for any of the devices that your firm manufactures.
16. Failure to maintain complaint files, and to establish and maintain standard operating procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198. For example, you stated that you stopped documenting complaints over a year ago, and there is no evidence that complaints 02-05-037, 02-06-004 and 02- 6-023 were reviewed or evaluated.
Make certain that your validation is up to regulatory compliance requirements by ensuring that this complete chain is in place.
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