FDA Warning for Inadequate Storage of Reference Samples and Reagents
Reference Samples and reagents should be stored according to manufacturers recommendations to maintain the required quality. FDA verifies storage conditions during inspections This became clear during an inspection of a drug manufacturer which resulted in a 483 with 12 observations.
Examples are: "Laboratory records do not include complete records of any testing and standardization of laboratory reference standards and reagents". "Biological Indicators were observed to be stored in Refrigerator on 06/22/10, which is not being monitored for storage at xx% RH as per manufacturers instructions" "Reagents were not logged into a drying Oven Log Book and were observed on 06/22/10 in the analytical room testing area desiccator. Reagents were stored in a crucible sealed with paraxin".
- Primary deviations: E-Records not "readily" available, impact of equipment failures on batch not investigated, inadequate follow up of complaints, only 5 system suitability test runs instead of 6, reference samples not stored under conditions as recommended by the manufacturer.
- Examples
-The 12-page 483 with 12 deviations lists 20 different document types together with the dates when the documents were requested and when they were available. Furthermore, the inspector found that "Stability information provided was not provided in an organized fashion on 06/30/10. I requested that the firm organize the information and bring in a computer on 07/02/10 to view the contents of xxx"..
- No Quality review was conducted concerning impact on batches that were manufactured during equipment failures. No maintenance records were completed describing what was done to fix the equipment. Equipment failures were not trended by Quality to determine the scope of the manufacturing equipment failures and the overall impact on the manufacturing process and products produced. No deviation report~ were generated, reviewed and approved by the firm's Quality Control Unit regarding the following manufacturing incidents.
- System suitability conducted for Dissolution Assay per laboratory test methods evaluates only five replicate injections for Relative Standard Deviation (RSD) NMT 3%. USP requires six replicate injections for instrument precision and accuracy
- Biological Indicators for lot were observed to be stored in Refrigerator on 06/22/10, which is not being monitored for storage at RH per manufacturers instructions.
- Routine inspection of mechanical and electronic equipment is not performed according to a written program designed to assure proper performance.
Specifically,
A. There is no Preventive Maintenance program for the following equipment in
a. Dissolution Apparatuses
b. xx for Rapid Resolution
c. Autotitratiorı
d. Spectrometer
e. UV/Vis Spectrophotometer