Understanding new regulations for HVAC validations

Berkshire Sterile Manufacturing

by Andrea Wagner



The FDA issued a new guidance document in 2011, General Principles and Practices for air filtration, which discusses the process validation of your HVAC systems.  21 CFR 211.46 for air filtration describes the HVAC system’s need to filter air into space and how it is controlled by this regulation. Most drug products are good promoters of microbial growth. Therefore concerns about how your HVAC system addresses temperature, humidity, and particulates are important.

The relatively new guidance replaces the common IQ/OQ/PQ that was typically done in the past and expands this into three stages.  It defines process validation as collection and evaluation of data from design to commercial production.

The three stages are:

Stage 1 – process design

Stage 2 – performance of the IQ/OQ/PQ

Stage 3 – Monitoring and maintenance, use of CAPA, PAT and change control as well as data collected in monitoring to continually improve the process

The system validation should be viewed as an HVAC system that controls the air that comes into contact with your drug products.

HVAC systems consists of three components:

  • Air handling Unit (AHU)
  • Air distribution system- duct work
  • Use areas


Stage 1 – Process Design

This stage looks at the user requirements and risk assessment.  You need to look at air flows and how materials are used.  Stage 1 produces functional specs, design specs, control strategy, and documents with user requirements and design specs that address the critical systems.  It also looks at how the control strategy was designed and references the mechanical and architectural drawings.


Stage 2Performance of the IQ/OQ/PQ

This stage focuses on performing the IQ, OQ, PQ of the system and the resulting documents are used to show the system meets the set criteria it was installed and built for.  The items that we qualify are the air handling system, distribution, control, temps, humidity, and pressurization as per classification.

In performing this work you will need engineering drawings, engineering specs, contractor’s submittals, O&M manuals, test and balance (TAB) reports.

When qualifying the utilities, as per the FDA guidance, a prioritization of the system is needed.  This is defined below:

  1. Installed correctly per parameters
  2. Capable of performing
  3. Report on the fact that it is acceptable for its use


Stage 3 – Monitoring and maintenance, use of CAPA, PAT and change control as well as data collected in monitoring to continually improve the process

The last stage, Stage 3, is continued verification.  This stage focuses on establishing an environmental monitoring system, collecting relevant data, and defining limits of alert and action to be analyzed at a set period to determine if the system remains in compliance.    Monitoring is required by 21 CFR 211.42-10(iv).  The monitoring program should look at the system’s ability to maintain temperature, humidity, pressure, particulate and microbial load at pre-defined acceptable levels.  This data needs to be evaluated and trends should be noted and investigated to ensure continued compliance.

For more information please contact Andrea Wagner at Berkshire Sterile Manufacturing.

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