FDA blasts California firm for multiple GLP issues involving nonclinical studies

Regulatory NewsRegulatory News
| 11 August 2022 | By Joanne S. Eglovitch 

The US Food and Drug Administration (FDA) found a slew of good laboratory practice (GLP) violations during the conduct of nonclinical studies at West Sacramento, CA firm Valley Biosystems in a 3 August warning letter and blasted the firm for not following its own procedures governing animal welfare, inadequate staff training, data integrity issues and inadequate reporting of nonclinical studies.
 
The warning letter was sent to the West Sacramento, CA, based firm over “objectionable conditions” observed during a late August to early October inspection that was conducted as part of the agency’s bioresearch monitoring program.
 
The seven-page warning letter cited the firm for five GLP violations.
 
FDA investigators said the firm lacked documentation that staff, including the chairman of the board, three veterinarians, a pathologist and operations manager, conducted the necessary training to conduct the nonclinical study for the investigational treatments. “Your firm failed to maintain records of trainings that your staff had received to adequately assess their competency and qualifications to perform their assigned tasks.”
 
The company failed to follow its own protocol concerning animal welfare. The protocol required that “signs of animal illness, injury, or pain and distress” should be communicated to the study director and sponsor monitors.” Yet “it was not documented that these requirements were met” for four sick animals, one with hemorrhagic diarrhea, and three animals that had Trichuris infection.
 
The firm also failed to retain the raw data generated from nonclinical laboratory studies. For example, there were missing anesthesia records for 12 of the 48 animals that underwent surgery. According to the firm’s quality assurance unit (QAU), the original paper records were discarded once they were scanned and saved electronically.
 
In addition, the firm “failed to preserve any source records demonstrating your study director’s adherence to the GLP requirements in regard to his conduct of writing the final reports” for the studies.
 
The firm was also cited for inadequate reporting of nonclinical laboratory results.  For example, the final report had three missing documents; a daily clinical observation for an animal demonstrating “nervous tapping;” a functional observation battery evaluation, or a post-dose out-of-cage assessment that found the animal experiencing “abnormal dysmetria” and “mild crouching of the torso when walking tripedally”; and a missing animal health record for an animal experiencing “acute emesis.”
 
Additionally, records from the laboratory that the firm contracted to perform histopathology and immunohistochemical analysis cited “numerous comments of poor-quality and insufficient tissue collections” sent by the firm.
 
For “Week-5” animals, various deficiencies were noted for all spinal cords, eye tissues, kidney tissues, heart tissues and larynx tissues.
 
“Various observations” were noted in the tissues of an unscheduled death of an animal, including the ureters, salivary gland, adrenal, heart, femur/sternum bone and marrow and kidneys.
 
For animals sacrificed at 13 weeks, brains were not received from a few animals, and only one liver was received from a group of four animals.
 
The firm was also lambasted for failure of the QAU to inspect each laboratory study to ensure the integrity of the study and maintain properly written records.
 
“Your QAU failed to maintain contemporaneously signed and dated documentation or reports of the Critical Phase inspections. Your QAU stated that the Critical Phase inspection results were written directly on the Protocol or on scratch pieces of paper that were thrown away after summarizing the results on the monthly Quality Assurance Status Reports.”
 
The company was given 15 days to respond to the letter, and failure to respond may result in regulatory action.
 
Warning letter
 

 

© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

4;5;13;20;26;31;