Cleanroom Controls in OSD Manufacturing

When people think of cleanrooms, they often picture sterile injectable medicines, with operators in full gowning working in Grade A or B environments. It is easy to assume that oral solid dose (OSD) manufacturing, with its tablets, capsules and powders, does not need the same level of rigour.

After all, OSD products are not sterile. But the reality is that cleanroom controls in OSD facilities are just just as critical, though the risks and priorities look different.

OSD Filling.

The Risks Unique to OSD

OSD manufacturing is dominated by powders. Powders generate dust, and dust presents two key risks.

First, there is the danger of cross-contamination between products. If traces of one active ingredient migrate into another product line, patients could be exposed to the wrong drug or an incorrect dose. In multi-product facilities, this is one of the biggest risks regulators look for.

Second, dust can compromise operator safety. Highly potent actives (HPAPIs), such as certain oncology drugs or hormones, can be hazardous at very low exposure levels.

Without proper containment and cleaning, operators themselves are at risk of inhalation or dermal exposure. In this sense, cleanroom controls are not just about protecting patients, they are also about protecting the workforce.

Regulatory Expectations

Regulators have made it clear that OSD facilities are expected to maintain high standards of contamination control. The FDA frequently cites firms for inadequate segregation of potent compounds, insufficient HVAC zoning, or poor cleaning validation.

The European Medicines Agency (EMA) and PIC/S emphasise the same themes, highlighting the need to design facilities that minimise the risk of cross-contamination.

Facilities that rely on inadequate controls, such as simple cleaning between batches of very different products, are unlikely to satisfy inspectors.

What Cleanroom Controls Look Like in OSD

While OSD facilities may not need aseptic filling suites, they do need carefully designed cleanroom environments. Some of the most important controls include:

• Zoning and Segregation: High-potency products often require dedicated rooms or suites, with physical barriers separating them from other operations. Even within standard production areas, zoning by pressure differentials and airflow direction helps prevent dust migration.

  
  

• HVAC Design: Air handling systems must be designed to prevent recirculation of contaminated air into other areas. Negative pressure rooms for potent actives are common, as are high-efficiency filters to capture fine particles.

  
  

• Cleaning Validation: Residues from powders can be difficult to remove, especially from equipment with complex geometries. Cleaning validation is therefore essential to show that residues are consistently reduced to safe levels.

• Containment Equipment: From isolators and split-butterfly valves to contained tablet presses, modern OSD facilities often use equipment that minimises operator exposure and product cross-contamination.

• Material and Personnel Flows: Well-designed flows reduce the risk of carrying contamination between areas. This includes airlocks for both materials and operators, along with clear gowning requirements.

The Human Factor

Cleanrooms are not just about technology.

People remain the biggest variable in any controlled environment. In OSD facilities, operator practices can easily make or break contamination control. Poor gowning discipline, shortcuts in cleaning, or mishandling of materials can all lead to problems.

Training is therefore vital. Operators need to understand not just the "how" but also the "why" behind procedures. Explaining that a tiny trace of cross-contaminant could trigger a patient reaction helps reinforce the importance of seemingly small actions.

A Cost-Effective Investment

Some firms still see enhanced cleanroom controls as a cost burden. But the reality is that strong contamination control saves money in the long run.

Recalls are expensive, reputations are fragile, and regulatory enforcement can shut down a facility altogether. By investing in cleanroom design, robust cleaning programmes, and staff training, OSD manufacturers can avoid these costly disruptions.

It is also worth noting that many OSD facilities now handle a wider range of products than ever before, from generic tablets to complex formulations with very low dose actives.

The more diverse the portfolio, the more critical cleanroom controls become.

Conclusion

Cleanrooms in OSD facilities may not look the same as those in sterile manufacturing, but they are no less important. By controlling dust, preventing cross-contamination, and protecting both patients and operators, they provide a foundation for safe and compliant production.

Regulators expect it, consumers rely on it, and brands ultimately benefit from the confidence it creates.

📌 Need help designing or remediating your contamination control program? 

Pharmalliance Consulting Ltd offers hands-on support, training, and gap assessments to ensure your OSD operations are regulatory-ready and quality-driven. Get in touch with our team of contamination control experts to start your compliance journey today.