GMP TRENDS, INC. | Example - Manufacturing-Sterile Product Controls


DISTRICT ADDRESS GMP Trends Inc. P.O. Box 8001 Boulder, Colorado 80306			DATE OF ISSUE Introductory
			C.I. ISSUE Issue # MMXIX
NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED To: Responsible Person, Director of Quality Assurance
FIRM NAME Pharmaceutical and Related Industries		STREET ADDRESS 5600 Regulation Lane
CITY, STATE AND COUNTRY United States of America and Worldwide		TYPE OF ESTABLISHMENT INSPECTED Pharmaceutical and Related Industries
During a review of inspection reports of U.S. firms (i) (we) observed: EDITED EXCERPTS FROM ACTUAL 483 OBSERVATION REPORTS BY FOOD AND DRUG ADMINISTRATION INVESTIGATORS Manufacturing-Sterile Product Controls .....Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during production. Specifically, SOP ....., Airflow Pattern Visualization Studies. The smoke study videos’ document airflow patterns of various work surfaces. However, the smoke studies do not completely document all of the dynamic operations that commonly occur during routine filling operations. For example, the Validation/Quality Department has performed an airflow evaluation for manufacturing room ..... that is used for the vial capping operations. However, a similar airflow evaluation has not been performed for manufacturing room ....., which is the area that is used to perform the manual aseptic connections of the sterile solution to the fill equipment in aseptic fill suite ..... .....There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed. Specifically, In support of the aseptic process, the Drug Master File (DMF .....) establishes ..... media fill specifications. However, in regard to media fill batches, there are no records to document the assignable cause for the rejection of media filled bottles, which precludes the Quality Unit from confirming that the media fills met the acceptance criteria. The Environmental Monitoring (EM) Trend data, documents the percent of microbial identification for Gram Positive Bacillus species, from the EM sampling for the manufacturing facility. The EM sampling identifies the locations where the microbial contaminants were recovered. However, the evaluations fail to identify the source(s) of the microbial contaminants. For example, the root cause for presence of the Bacillus species contamination. The root cause evaluations(s) in turn assist to address, and ultimately control, the ingress of objectionable microorganisms. .....Equipment used in the manufacture, processing or holding of drug products is not periodically tested to ensure that functional capabilities are maintained. There is no periodic testing of the Sterile Depyrogenation Tunnel to ensure that a Class 100 environment is maintained in the depyrogenation tunnel. The Operational Qualification (OQ) included acceptance criteria performed to ensure that particulate levels meet the requirements for Firm’s Level I (Class 100) conditions. Furthermore, there has been no testing to ensure that the differential pressures are properly maintained between the inlet zone, hot zone and cooling zones. The depyrogenation oven is used to prepare vials for aseptic filling area ..... The depyrogenation tunnel has been used in production since ..... .....Written production and process control procedures are not followed in the execution of production and process control functions. Specifically, the “Interrupted Fill Events” SOP ....., established the practice of Change Requests. Three interrupted fills have occurred since the initiation of the Change Requests and establishment of the above mentioned Standard Operating Procedure. However, the Director of Regulatory Affairs confirmed there is no language in the drug application concerning the interrupted fills strategy/option with respect to their process validation. In addition, the interrupted fill practice and the option of interrupting the currently approved aseptic filling process as well as the effect(s) on the process validation submitted in the drug application has not been communicated or submitted to the FDA for review.
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Manufacturing-Sterile Product Controls

.....Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during production.

.....There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed.

.....Equipment used in the manufacture, processing or holding of drug products is not periodically tested to ensure that functional capabilities are maintained.

.....Written production and process control procedures are not followed in the execution of production and process control functions.