USFDA 483 Observations – Top 5 Common Observations

USFDA 483 Observations – Top 5 Common Observations

• Quality control procedures not in writing fully followed
• Scientifically sound laboratory controls not established
• Investigations of discrepancies, failures to adequately review
• Absence of Written Procedures for production and process controls
• Written procedures not established/followed for cleaning and maintenance equipment
• Lack of or inadequate procedures (CAPAs)
• Lack of or inadequate complaint procedures
• Purchasing controls, Lack of or inadequate procedures to ensure that all purchased product conforms to specifications Lack of Written MDR Procedures
• Lack of or inadequate process validation
• Lack of Written MDR Procedures
• Nonconforming product, Lack of or inadequate procedures.
• Environmental Monitoring System deficient

Lack of controls to prevent contamination of drug products – Facilities that pose a significant microbial contamination risk.

For example-

Poor facility maintenance, including leaking pipes in the cleaning room ceiling, chipped and cracked floors in the batch tank room, and blue and black particulates as well as dust on tanks next to the ingredient charging ports

Failure to thoroughly investigate contamination, and releasing lots without meaningful scientific justification. (A negative retest, alone, is NOT sufficient).

The firm identified microbial contamination with a positive test result, yet distributed the lots that tested positive after a “clean” retest without a scientific basis to invalidate positive test results

• No evidence of lab error
• Failure to recognize that it is typical for contamination to be distributed non-uniformly in a batch
• Failure to identify a root cause of the contamination and setting forth a scientific rationale to discount the firm’s production operation was not the source of the microbial contamination.

The top 4 most common observations for drugs

1. Quality control procedures not in writing fully followed
2. Scientifically sound laboratory controls not established
3. Investigations of discrepancies, failure to adequately review
4. Absence of written procedures for production and process controls

The top 2 most common observations for devices

1. Lack of or inadequate procedures (CAPAs)
2. Lack of inadequate complaint procedures
3. Lack of Written MDR Procedures and Purchasing controls, Lack of or inadequate procedures to ensure that all purchased product conforms to specifications