Top FDA Form 483 Observations: HVAC

This blog highlights key FDA Form 483 observations on HVAC in pharmaceutical manufacturing. Issues include improper cleaning, lack of written procedures, and failure to follow qualification protocols. Root causes include procedural gaps and oversight, with corrective actions like revising protocols, conducting risk assessments, and ongoing training to maintain compliance and prevent cross-contamination or data integrity issues.

1. Ventilation systems, including equipment for control of air pressure, are not adequately designed and constructed to minimize risks of contamination.

Summary
Inadequate HVAC and monitoring systems lead to pressure excursions and potential contamination risks in the production suites.
Excerpt from Observation
The heating, ventilation, and air conditioning (HVAC) system used to establish the specified differential pressure between the production suites and the neighboring outside environment are not sufficient.

Justification
The HVAC system's adequacy directly impacts the ability to maintain critical pressure differentials to prevent contamination.

Possible Root Cause
HVAC system not designed to sustain specified pressure differentials under varying operational conditions.

Corrective Actions
Upgrade HVAC system to ensure it can maintain required pressure differential levels consistently.

Preventive Actions
Implement periodic maintenance and validation protocols for the HVAC system.

View detailed analysis of this observation 

Reference FDA 483:
Company Name: Taenaka Kogyo Co., Ltd.
Issue Date: 2024-04-12
Inspection Dates: 08-04-2024 to 12-04-2024
Investigators: Christopher R Czajka

2. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the aseptic process.

Summary
Inadequate validation of sterile drug manufacturing processes.

Excerpt from Observation
Qualification of the HVAC system...did not demonstrate it can maintain appropriate air quality for aseptic filling...smoke studies have not evaluated if air flow...would allow air ingress...

Justification
The observation indicated deficiencies in HVAC system validation, especially concerning air quality and particle control in aseptic environments.

Possible Root CauseInsufficient validation and dynamic assessments of the HVAC system, leading to potential contamination risks during aseptic filling.

Corrective Actions
Perform comprehensive HVAC system re-qualification, including dynamic condition assessments and HEPA coverage evaluations.

Preventive Actions
Implement routine HVAC system checks and dynamic smoke studies, ensuring robust documentation and immediate corrective actions upon deviations.

View detailed analysis of this observation

Reference FDA 483:
Company Name: Eugia Pharma Specialities Limited
Issue Date: 2024-02-02
Inspection Dates: 22-01-2024 to 02-02-2024
Investigators: Justin A Boyd, Eileen A Liu, Anastasia M Shields

3. Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable size and construction to facilitate cleaning, maintenance, and proper operations

Summary
Facility design does not support proper operations, maintenance, and cleaning, compromising product sterility.

Excerpt from Observation
It was observed that quality unit documentation failed to demonstrate control over differential pressure in your production core to maintain aseptic conditions.

Justification
Maintaining appropriate differential pressure is essential in controlling contamination risks, as highlighted in the observation.

Possible Root Cause
Lack of effective monitoring and control mechanisms for the HVAC system leading to deviations in the differential pressure.

Corrective Actions
Immediate recalibration of HVAC system to ensure it meets specified differential pressures. Conduct comprehensive requalification of the system.

Preventive Actions
Establish a robust HVAC monitoring and maintenance schedule, with regular calibration checks and real-time monitoring.

View detailed analysis of this observation

Reference FDA 483:
Company Name: Eugia US Manufacturing LLC
Issue Date: 2023-12-22
Inspection Dates: 11-12-2023 to 22-12-2023
Investigators: James R Birkenstamm, Daniel L Zheng, Ruben C Quintana, Yoriann M Cabrera Bartolomei

4. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not written.

Summary
Operators failed to maintain aseptic techniques and cleanroom airflow was obstructed, compromising microbiological contamination control.

Excerpt from Observation
Air return vents for the firm’s HVAC system were observed to be obstructed.

Justification
HVAC is applicable because proper airflow is critical to maintaining aseptic conditions.

Possible Root Cause
Inadequate enforcement of SOP SAN-002-W regarding the obstruction of air return vents.

Corrective Actions
Immediately clear all obstructions from HVAC air return vents and inspect for compliance.

Preventive Actions
Regularly inspect and enforce storage practices to ensure vents are unobstructed, and update SOPs for clarity if needed.

View detailed analysis of this observation

Reference FDA 483:
Company Name: SCA Pharmaceuticals, LLC
Issue Date: 2023-10-20
Inspection Dates: 18-09-2023 to 20-10-2023
Investigators: Jonah S Ufferfilge, John P Mistler

5. HEPA filters are not sealed around the perimeter.

Summary
Unsealed HEPA filters in ISO 7 rooms compromise clean air supply.

Excerpt from Observation
HEPA filters in the ISO 7 non-hazardous room were not properly sealed. The perimeter of the HEPA filter did not overlap to the ceiling.

Justification
The HVAC system directly impacts the proper sealing and placement of HEPA filters, which are essential for maintaining the required air quality.

Possible Root Cause
The fundamental cause appears to be a failure in facility maintenance protocols, particularly the routine inspection and maintenance of HEPA filter installations.

Corrective Actions
Immediately reseal or replace all unsealed HEPA filters in the ISO 7 non-hazardous room. Conduct a comprehensive inspection of all HEPA filters to ensure proper sealing and functionality.

Preventive Actions
Implement a stringent protocol for routine inspection and maintenance of HVAC systems, including HEPA filters. Train personnel on proper installation and maintenance techniques for HEPA filters.

View detailed analysis of this observation

Reference FDA 483:
Company Name: New Vitalis Pharmacy LLC dba New Vitalis
Issue Date: 2023-07-05
Inspection Dates: 12-06-2023 to 05-07-2023
Investigators: Ucheabuchi C Chudi-Nwankwor

Effective Strategies to Prevent FDA 483 Observations

• Stay updated on FDA regulations: Ensure thorough knowledge of the latest GMP and quality control standards.
• Conduct regular internal audits: Proactively assess compliance to identify and correct potential issues.
• Maintain accurate documentation: Keep batch records, SOPs, and logbooks complete, current, and readily accessible.
• Implement a strong CAPA system: Address deviations swiftly through Corrective and Preventive Actions.
• Conduct mock FDA inspections: Practice readiness by simulating inspections to uncover any gaps.
• Ensure facility and equipment maintenance: Keep facilities clean and organized, with properly calibrated equipment.

Leverage QMS Software to Prevent FDA 483 Citations

An effective QMS software can help you stay ahead of compliance challenges by automating quality processes, ensuring accurate documentation, and providing real-time oversight. With Leucine’s QMS, companies can seamlessly manage deviations, implement proactive CAPA systems, and always be inspection-ready, significantly reducing the risk of receiving FDA 483 citations.