Pharmaceutical companies are under constant pressure to reduce operating costs without compromising product quality. There are a number of factors that affect operating costs, and energy prices are one of many. Global fuel and energy prices remain volatile due to geopolitical issues. The U.S. Energy Information Administration reported that global oil markets remain in a period of “heightened volatility and uncertainty,” with Brent crude averaging $105/barrel (€95, £80, or ₹8,8076 estimated equivalent global currencies) in May 2026 (Short-Term Energy Outlook – U.S. Energy Information Administration (EIA)) amid supply disruption and inventory pressure. In that environment, it is understandable that manufacturers are looking closely at one of the largest utility consumers in facilities which is Heating Ventilation Air Conditioning (HVAC).

One common energy-saving strategy is an HVAC setback. In recognized HVAC practice, “night setback” (or unoccupied setback) means allowing indoor conditions to drift away from occupied setpoints during periods of inoccupation so that heating, cooling, and ventilation equipment can operate less frequently or even shut down. However, this can pose a hazard in pharmaceutical manufacturing if the simple question “Can we save energy and maintain the qualified state?” does not have a balanced approach. In addition, this question may have different answers for each geography where a firm has a site (think of Singapore vs Canada).

A risk can emanate from the misconception that pharmaceutical HVAC systems are designed only for comfort. HVAC plays an important role in prevention of contamination; prevention of cross-contamination is an essential HVAC design consideration. Airflow rates, air change rates, filtration, room pressure cascades (positive or negative), temperature, humidity, and recovery time are often interconnected. Reducing supply airflow during off-hours may also reduce return airflow, exhaust balance, room pressurization, and the intended direction of air movement. A small change in fan speed or damper position can shift differential pressures across multiple rooms because cleanrooms, corridors, airlocks, returns, exhaust branches, and pressure-controlled zones are hydraulically connected.

This is especially important where room differential pressure is part of a larger contamination control strategy. FDA’s aseptic processing guidance emphasizes proper airflow from areas of higher cleanliness to adjacent less clean areas and recommends substantial positive pressure differential between rooms of differing classification. ISPE summarizes regulatory expectations for rooms classified as B, C, and D (Room Differential Pressures in Facility Design: Fundamentals | Pharmaceutical Engineering); however, other areas such as warehouses, retain sample rooms, loading docks can also be particularly vulnerable where even ambient temperature control can be at risk with HVAC setbacks.

In situations where HEPA filters are used in conjunction with the HVAC, setbacks can put at risk the required face velocities determined while testing or even a room’s cleanup time, particularly when night shift GMP cleaners may be more active in preparation for the next shift. Conversely, setbacks do not automatically “fail” a HEPA filter integrity certification, because HEPA leak testing evaluates the installed filter system for leaks or bypass under defined test conditions. However, reducing airflow could put the certified operating state at risk if the HEPA filters, terminal housings, airflow velocities, room air-change rates, recovery performance, particle counts, or pressure differentials were certified at a higher airflow condition than the new setback/recovery mode. In other words, the filter may still be intact, but the cleanroom may no longer be operating under the documented qualified conditions.

What can you do before introducing Setbacks?

  • Open formal change control for any BAS schedule, fan speed, damper, airflow, pressure, or unoccupied mode change. Ensure impact to any existing Contamination and Control Strategy (CCS) is considered.
  • Perform GMP risk assessment using room classification, product exposure, potency/toxicity, contamination risk, and cross-contamination risk.
  • Review HVAC design basis: URS, DQ, airflow diagrams, pressure cascade drawings, AHU zoning, exhaust dependencies, and airlock strategy.
  • Define setback boundaries: which rooms may be reduced, which must remain fully operational, and whether classified/core manufacturing areas are excluded.
  • Model or test pressure impacts across adjacent rooms, corridors, airlocks, gowning areas, material/personnel flows, and exhaust-controlled rooms.
  • Verify recovery time before production restarts, including temperature, humidity, differential pressure, particle counts, and viable monitoring where applicable.
  • Assess HEPA certification impact: determine whether existing HEPA integrity, airflow velocity, airflow volume, and cleanroom classification tests remain representative of the new operating state.
  • Requalify as needed: airflow volume, ACPH, room pressure cascade, smoke studies, particle classification, recovery testing, alarms, and HEPA leak testing if airflow conditions materially changed.
  • Update SOPs and BAS controls to prevent unauthorized schedule overrides and to require documented return-to-normal verification before GMP operations.
  • Trend environmental data before and after implementation to prove the energy-saving mode does not degrade contamination control.

The bottom line: HVAC setbacks can reduce cost, but in pharmaceutical manufacturing they must be treated as a GMP change—not a facilities optimization. If the airflow reduction changes the conditions under which the area or HEPA system was qualified, the company should assume the validated state may be at risk until proven otherwise. If you need assistance in evaluating the impact of any proposed change of your HVAC systems on your operations, please contact us at LCS@lachmanconsultants.com.