FDA form 483 observations: NATCO Pharma

General Information:

• Company: NATCO Pharma Limited, Pharma Division, Kothur Village, Rangareddy,         Telangana, India

• Inspection Dates: 06/09/2025 - 06/19/2025

• Products manufactured:

Sterile and Non-Sterile Drug Manufacturers 

Oral solid dosages, including Cytotoxic Orals

Cytotoxic Injectables

Pre-filled Syringes

Key Observations: 1. Environmental Monitoring Deficiencies (Observation 1):

• The firm's system for monitoring environmental conditions in aseptic processing areas is deficient.
• Electronic data for non-viable particle (NVP) counts used in environmental monitoring and cleanroom qualification is not adequately reviewed.
• Discrepancies exist between electronic data and official hardcopy results for NVP, affecting multiple batches between 11/02/2023 and 04/16/2024, where results were altered.
• Operators saved data on USB drives, potentially allowing data manipulation, which indicates a gap in data integrity.
• The firm failed to follow its standard operating procedure (SOP) for handling out-of-limit NVP results for certain injection batches between 04/16/2024 and 06/06/2025.
• Locations with initial failing results were repeatedly sampled until passing results were obtained, without initiating incident reports or investigations. This deviation from the SOP was not identified or addressed, demonstrating inadequate quality oversight.
• In multiple instances, the first sample failed, and the sample was subsequently retested and passed, but there was no documentation by operators to indicate whether the failures were due to personnel movement, making it impossible to verify if the retesting was justified according to the procedure.
• Environmental monitoring data during aseptic operations was not always printed and attached to batch records.
• Environmental monitoring activities in the change room were not properly documented and reviewed; many data reports were not printed, documented, or reviewed.

2. Equipment Maintenance (Observation 2):

• Equipment and utensils are not maintained at appropriate intervals to prevent contamination.
• Discrepancies were observed in the aseptic processing area, including:

• Damage on the wall above and below the clean room phone panel in the Grade A extended laminar airflow (LAF) area at the start of the RABS (Restricted Access Barrier Systems).
• Exposed bolt threads in the Grade A LAF.
• Gaps and rough edges on both corners of the extended LAF frame by the sealing machine.o Torn bottom of the used to extend the entry frame in Grade A RABS number.
• Gap between the RABS frame and the Grade A RABS number.

3. Aseptic Process Validation (Observation 3):

• Procedures to prevent microbiological contamination of drug products lack sufficient validation of the aseptic process.
• Review of dynamic condition smoke study videos revealed discrepancies, including:
• Limited portions of the RABS were visible due to camera angles.
• The smoke generation device was not visible, which prevented identifying airflow patterns.
• Videos did not include adequate smoke to determine airflow patterns.
• The smoke study report included comments about the need to reshoot videos, but various departments signed off on each video as meeting acceptance criteria.
• Turbulent air was identified during the RABS intervention, but the video was still signed off as meeting the acceptance criteria.
• The firm does not incubate all integral vials during media fills and uses a method for conducting seal integrity checks on only a portion of integral vials per media fill, which is not representative.

4. Review of Discrepancies (Observation 4):

• Failure to thoroughly review unexplained discrepancies.
• A disinfectant efficacy study was not performed when a new microorganism was identified during an OOS investigation for environmental monitoring.
• During review of Non-Viable Particle Count environmental data generated during aseptic operations for batches, the exact locations were sampled multiple times with failing results until a passing result was eventually obtained.
• Interruptions occurred in Empower 3 projects in the form of project integrity failures, including instances where injections were interrupted and then the sample set sequence was restarted without proper documentation or investigation.

5. Microbiological Contamination (Observation 5):

• Procedures to prevent microbiological contamination are not established, written, and followed.
• The firm does not have any employees fully qualified to perform 100% visual inspection activities on sterile drug products.

6. Building Construction (Observation 6):

• The aseptic processing area is not adequately visible from the viewing windows.

7. Quality Control Unit (Observation 7):

• The responsibilities and procedures applicable to the quality control unit are not in writing and are not thoroughly followed.
• The Quality Unit has not demonstrated a clear understanding of communication errors during HPLC and GC testing.
• A retrospective review of cGMP compliance sufficiency revealed extraneous peaks, and a new protocol was established. However, the results of this review have not yet been assessed.
• The firm's quality system does not ensure that all investigations are properly documented and retained, as draft investigations were discarded through shredding without proper documentation.
• The Quality unit has failed to properly document and review environmental monitoring activities conducted during aseptic manufacturing operations.

Some of the observations could be a bit challenging to address, and the Company might work hard to avoid a Warning Letter.