An HVAC system used in pharmaceuticals might work properly on a normal day, but if the weather conditions become more difficult, it will cause troubles for the HVAC system as well. Both extreme heat and overly low temperatures could influence the pressure within the room, as well as influence temperature stabilization, humidity control, air changes, and cleanroom efficiency.
This is the reason for seasonal qualifications of HVAC systems to be highly relevant for GMP manufacturing facility maintenance. The goal of the process is not to re-qualify the entire system each season but to show that the system remains compliant with its design and operating characteristics even under the worst environmental conditions.
It is interesting to note that during inspections, inspectors do not really pay that much attention to whether seasonal qualification was performed or not. Instead, they are more interested in observing how seasonal strategy was justified, results were documented, and deviations were handled.
Seasonal qualification is performed to confirm the proper performance of the following parameters of the HVAC system:
Typical areas include aseptic manufacturing suites, clean rooms and clean benches, preparation areas for sterile parts, and weighing and dispensing areas.
Engineering should also evaluate critical air handlers, chilled water systems, heating coils, humidity control equipment, and building management systems because failures in these systems may affect some critical manufacturing area as well.
A typical summer qualification process consists of checking whether the HVAC system can maintain the temperature and humidity in the room during periods of peak load.
Temperatures and humidity stability, controlling delta pressure, HEPA airflows, recovery from opening the doors, handling condensate, alert systems - these are some of the key parameters.
One thing I would always pay attention to is the relationship between the humidity excursions with delta pressure. Too much moisture can affect airflow balance.
Heating system must provide comfortable and qualified environment without causing excessive dryness which may influence both product manufacturing and comfort of personnel. In case of manufacturing of hygroscopic material, reduction of humidity might also influence production in an unpredictable way.
Usually, winter qualification concentrates on temperature recovery, stability of humidity, pressure cascade, heating coil work, fresh air control and environmental monitoring trends.
Acceptance criteria must comply with the qualification protocol and not be changed only due to the change of weather conditions.
Usually, the protocol mentions HVAC systems, qualified zones, testing seasons, environmental conditions, measuring instruments, sampling points, acceptance parameters, responsibilities, deviations, and reporting requirements.
It is also important to specify whether the tests are going to be conducted under operational, at-rest, or dynamic conditions.
This aspect gets extremely relevant in sterilized environments since actual presence and operation may alter the airflow behavior.
Some of the documentation to take into consideration is:
If the humidity level of the dispensing room goes higher than its acceptable limit only for 20 minutes in the summer, then an investigation should determine the cause of deviation (such as equipment failure, door usage, maintenance, utility failure, error with sensor, or operational issue).
An investigation should answer the following three questions:
This kind of preparation helps to prevent problems resulting in unsuccessful qualification due to improper documentation or readiness of the equipment instead of malfunctioning HVAC systems.
For example, in case summer qualifications show prolonged humidity recovery time, Engineering should investigate whether there are any changes in chilled water capacity, dehumidification system performance, air handler unit load, or filter resistance.
The trend analysis is used as an early diagnosis tool to predict any decline in performance before it happens needs to be reported to the regulatory authorities.
Hence, HVAC systems are expected to continue their proven performance through adequate qualification, proper monitoring and maintenance, as well as timely review of performance throughout the whole lifecycle rather than relying upon initial qualification results.
An effective seasonal qualification program contains technical testing, measurement, documentation, monitoring or trend analysis and investigation of non-conformance. Only when all of these elements are combined, the company can demonstrably prove the ability of its HVAC system to keep the validated state of GMP manufacturing setup in operation at all time.
It is interesting to note that during inspections, inspectors do not really pay that much attention to whether seasonal qualification was performed or not. Instead, they are more interested in observing how seasonal strategy was justified, results were documented, and deviations were handled.
Understanding Seasonal Qualification
Seasonal qualification refers to a systematic evaluation of HVAC system performance during seasonal operation periods in summer and winter. The utility of this process is to verify that the HVAC system continues to perform the same way under varying external temperature and humidity conditions.Seasonal qualification is performed to confirm the proper performance of the following parameters of the HVAC system:
- Room temperature
- Relative humidity
- Differential pressure
- Air changes per hour (ACPH)
- Air flow patterns
- HEPA filter efficiency
- Restoration of the system after deviations
Which Areas Should Be Included?
Not all spaces in a facility will require the same focus on seasonal assessment. The key focus should always be on areas that are GMP-critical where environmental conditions have a direct impact on quality.Typical areas include aseptic manufacturing suites, clean rooms and clean benches, preparation areas for sterile parts, and weighing and dispensing areas.
Engineering should also evaluate critical air handlers, chilled water systems, heating coils, humidity control equipment, and building management systems because failures in these systems may affect some critical manufacturing area as well.
Summer Qualification: The Real Challenge is Humidity
In many pharmaceutical organizations, summer brings the greatest challenge to HVAC systems. High outdoor humidity levels increase the load on dehumidifying systems, while frequent door opening adds moisture into the space.A typical summer qualification process consists of checking whether the HVAC system can maintain the temperature and humidity in the room during periods of peak load.
Temperatures and humidity stability, controlling delta pressure, HEPA airflows, recovery from opening the doors, handling condensate, alert systems - these are some of the key parameters.
One thing I would always pay attention to is the relationship between the humidity excursions with delta pressure. Too much moisture can affect airflow balance.
Winter Qualification Presents Different Risks
Winter qualification is very important because low survival temperature lead to various difficulties in operation.Heating system must provide comfortable and qualified environment without causing excessive dryness which may influence both product manufacturing and comfort of personnel. In case of manufacturing of hygroscopic material, reduction of humidity might also influence production in an unpredictable way.
Usually, winter qualification concentrates on temperature recovery, stability of humidity, pressure cascade, heating coil work, fresh air control and environmental monitoring trends.
Acceptance criteria must comply with the qualification protocol and not be changed only due to the change of weather conditions.
What Should the Qualification Protocol Include?
A good protocol should make clear the reason of carrying out seasonal tests and what evidence will help establish that the qualification process has been successful.Usually, the protocol mentions HVAC systems, qualified zones, testing seasons, environmental conditions, measuring instruments, sampling points, acceptance parameters, responsibilities, deviations, and reporting requirements.
It is also important to specify whether the tests are going to be conducted under operational, at-rest, or dynamic conditions.
This aspect gets extremely relevant in sterilized environments since actual presence and operation may alter the airflow behavior.
Documentation That Inspectors Commonly Review
Seasonal Qualification doesn’t just produce one report. In fact, supporting documentation is sometimes equally as important as the qualification report.Some of the documentation to take into consideration is:
- Approved qualification protocol
- Calibration Certificates of measuring instruments
- Temperature and humidity mapping
- Differential pressure records
- Air velocity and flow measurements
- HEPA integrity test reports
- Environmental monitoring trends
- BMS records
- Alarm history
- Findings and CAPA
- Final qualification report
Managing Seasonal Qualification Deviations
Seasonal deviations do not all necessarily cause the need for requalification of the HVAC system at the facility.If the humidity level of the dispensing room goes higher than its acceptable limit only for 20 minutes in the summer, then an investigation should determine the cause of deviation (such as equipment failure, door usage, maintenance, utility failure, error with sensor, or operational issue).
An investigation should answer the following three questions:
- What was the reason for excursion?
- Has it affected GMP processes and quality of product?
- Is the validated state still acceptable?
Practical Readiness Checklist Before Seasonal Testing
QA team and Engineering department need to ensure that the system is genuinely ready for assessment rather than taking for granted that the successful outcome of previous assessment is an indication of readiness.| Checkpoint | Verification |
| HVAC preventive maintenance | Completed and documented |
| HEPA filter integrity | Current qualification available |
| Differential pressure gauges | Calibrated |
| Temperature & RH sensors | Within calibration period |
| BMS alarms | Functional and verified |
| Airflow balancing reports | Current and approved |
| Qualification protocol | Approved before execution |
| Measuring instruments | Traceable calibration certificates |
| Cleanroom status | Qualified for testing conditions |
| Previous seasonal deviations | CAPA completed and reviewed |
This kind of preparation helps to prevent problems resulting in unsuccessful qualification due to improper documentation or readiness of the equipment instead of malfunctioning HVAC systems.
Incorporating Seasonal Qualification into the Validation Lifecycle
The concept of seasonal qualification should not be perceived as just a once-a-year event. The most successful programs do not regard seasonal qualification as a standalone activity but include it in ongoing activities such as periodic review, change management, environmental monitoring, utility data analysis, preventive maintenance, and risk assessment.For example, in case summer qualifications show prolonged humidity recovery time, Engineering should investigate whether there are any changes in chilled water capacity, dehumidification system performance, air handler unit load, or filter resistance.
The trend analysis is used as an early diagnosis tool to predict any decline in performance before it happens needs to be reported to the regulatory authorities.
Regulatory Perspective
According to the expectations of EU GMP Annex 15, it is required that establishments and their utilities be in a constant state of qualification throughout their lifecycle, while the principles of quality risk management explain the rationale for risk-based decisions regarding qualification and its continuing verification in ICH Q9 (R1).Hence, HVAC systems are expected to continue their proven performance through adequate qualification, proper monitoring and maintenance, as well as timely review of performance throughout the whole lifecycle rather than relying upon initial qualification results.
An effective seasonal qualification program contains technical testing, measurement, documentation, monitoring or trend analysis and investigation of non-conformance. Only when all of these elements are combined, the company can demonstrably prove the ability of its HVAC system to keep the validated state of GMP manufacturing setup in operation at all time.
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