Achieving clean room certification for 503A and 503B compounding pharmacies requires strict compliance with regulatory standards like USP <797>, USP <800>, and the FDA's cGMP guidelines. Here’s a quick breakdown of the process:

• 503A Pharmacies: Focus on USP standards and state regulations for individual prescriptions.

• 503B Facilities: Adhere to stricter cGMP standards due to large-scale production.

Key Clean Room Requirements:

• Must meet ISO Class 7 standards (≤10,000 particles >0.5 microns/m³).

• Maintain positive air pressure (≥0.01 inches) and specific environmental conditions (20-24°C, 30-60% humidity).

7 Steps to Certification:

1. Review Facility Status: Assess HVAC systems, layout, and compliance gaps.

2. Plan Clean Room Layout: Optimize workflows and install air systems.

3. Build and Install: Use compliant materials (e.g., epoxy panels, HEPA filters).

4. Set Up Monitoring: Track air quality, temperature, and humidity continuously.

5. Write Procedures: Establish cleaning, gowning, and hygiene protocols.

6. Train Staff: Provide role-specific training and regular assessments.

7. Complete Certification: Conduct self-inspections and schedule official audits.

Quick Comparison: 503A vs. 503B Requirements

Following these steps ensures compliance, patient safety, and long-term operational success.

Cleanroom Certification | USP 795 & 797 Revisions

1. Review Facility Status

Conducting a detailed review of your facility is crucial to ensure your clean room complies with USP and cGMP certification standards. This process highlights any adjustments needed to meet certification requirements.

Check Current Setup

A proper review should focus on the essential components that influence clean room performance. According to the Controlled Environmental Testing Association (CETA) guidelines, key areas to evaluate include:

• HVAC and Environmental Controls: Examine systems for air handling, filtration, temperature, humidity, and pressure.

• Facility Layout and Equipment: Assess the workspace, workflow, and equipment for compliance.

Your facility must meet specific technical standards, such as those outlined below:

Set Clean Room Type

Identify whether your facility needs a sterile (ISO Class 7 with positive pressure) or hazardous (negative pressure with dedicated ventilation) compounding area based on your operations. Ensure the setup complies with ISO Class 7 standards and other regulatory requirements.

Perform airflow studies and environmental tests to pinpoint performance gaps. Consider involving clean room consultants to address design and compliance challenges early on.

Once you've completed a detailed assessment of your facility, the next step is to design a clean room layout that aligns with these regulatory standards.

2. Plan Clean Room Layout

A well-thought-out layout does more than meet compliance standards - it helps streamline operations and minimizes the chances of certification delays. This stage requires a focus on both design details and air handling systems.

Collaborate with Clean Room Specialists

Bringing in clean room experts can ensure your layout meets regulatory requirements while optimizing workflows and integrating air systems. Look for professionals experienced with 503A and 503B facilities who are well-versed in CETA guidelines. It's important to check their track record with similar projects and their familiarity with current USP standards.

Some key design factors to keep in mind include:

• Unidirectional workflow to minimize cross-contamination

• Strategic placement of pass-through cabinets for efficiency

• Proper equipment spacing to allow for effective air circulation

• Non-shedding, easy-to-clean materials to minimize particle generation

Install Air Systems

Environmental controls are critical for meeting USP <797> and <800> standards. The clean room should maintain temperatures between 62-64°F, relative humidity of 45-55%, and 30-40 air changes per hour for ISO Class 7 conditions.

Essential HVAC components include:

• Primary Engineering Controls (PECs):

  • HEPA-filtered laminar flow hoods

  • Biological safety cabinets

  • Containment isolators

• Secondary Engineering Controls (SECs):

  • Systems for room pressurization

  • Temperature monitoring tools

  • Humidity control systems

With the layout and air systems finalized, you’ll be ready to move on to construction and installation to bring your clean room to life.

3. Build and Install

Building and installing your clean room correctly is key to meeting regulatory standards and maintaining the required environmental conditions for certification.

Choose the Right Clean Room Materials

Select materials that align with USP <797> and <800> standards to ensure cleanliness and compliance.

Here’s a quick guide to recommended materials:

Install Key Components

Pay attention to these critical aspects during installation:

• Air Handling Systems: Ensure proper placement and sealing of filtration units to meet ISO Class 7 standards.

• Pass-Through Chambers: Use airlocks with effective sealing to prevent contamination.

• Monitoring Equipment: Place particle counters and environmental sensors in optimal locations.

• Support Infrastructure: Set up reliable utilities with backup systems for uninterrupted operation.

Maintain a temperature range of 68°F to 72°F and relative humidity levels between 30% and 60%.

"Documentation is crucial for ensuring that all components are properly installed and verified. This includes maintaining records of material specifications, installation procedures, and testing results".

Once construction is complete, the focus shifts to setting up strong monitoring systems to ensure compliance over time.

4. Set Up Monitoring Systems

After arranging the clean room layout and installing the air system, the next step is setting up monitoring systems. These systems are essential for spotting problems early and ensuring sterility conditions remain intact.

Monitor Air Quality

To meet ISO Class 7 standards, keep a close eye on temperature, humidity, air changes, and particle counts. Aim for 35-40 air changes per hour, which provides a safety margin above the minimum of 30 air changes per hour required for ISO Class 7 environments.

Use tools like surface sampling, air sampling devices, and settle plates to track microbial contamination in key areas.

Create Testing Schedule

Design a monitoring schedule that aligns with USP <797> guidelines:

"Data from monitoring systems can be used to identify trends and potential issues, allowing for proactive adjustments to maintain optimal clean room conditions".

Set up clear protocols to handle contamination, including immediate alerts, shutdowns, decontamination steps, and root cause analysis. A digital monitoring system with real-time alerts can help you respond quickly if any parameter goes outside the acceptable range.

Keep detailed records of all monitoring activities - this includes parameter readings, test results, equipment calibration, and corrective actions. Make sure to validate your monitoring system to confirm its accuracy.

Once monitoring systems are in place, the next step is to establish clear clean room procedures for consistent compliance.

5. Write Clean Room Procedures

Consistent procedures are key to meeting and maintaining certification requirements. Once monitoring systems are in place, detailed clean room procedures become essential.

Set Cleaning Rules

Create specific cleaning protocols that outline the methods, frequencies, and approved agents for every area. Here's an example:

Ensure cleaning starts with the cleanest zones (like ISO Class 5 areas) to avoid cross-contamination.

Make Staff Hygiene Rules

Establish strict hygiene protocols that meet ISO standards. These should include detailed steps for gowning, contamination prevention, and documentation.

1. Gowning Sequence

• Wash hands with antimicrobial soap for at least 30 seconds.

• Follow the correct order for putting on PPE: booties, hair cover, face mask, and sterile gloves.

• Use PPE appropriate for the clean room's classification.

2. Contamination Prevention

• Ban cosmetics, jewelry, and personal items.

• Require regular hand sanitization between tasks.

• Enforce proper movement to reduce particle generation.

3. Documentation Requirements

• Maintain daily gowning logs.

• Use checklists to verify personal hygiene.

• Conduct regular competency assessments.

Keep these procedures accessible - either through digital systems or laminated copies at entry points. Update them every six months to stay aligned with current regulations and industry standards.

Once the procedures are in place, the focus shifts to training staff to follow these protocols effectively.

6. Train Clean Room Staff

Effective training is key to ensuring staff consistently meet the standards needed for clean room certification. It plays a direct role in maintaining compliance with required procedures and quality benchmarks.

Focused Training and Evaluation

Provide training tailored to each team member’s specific role. Cover essential areas like gowning procedures, equipment handling, contamination prevention, cleaning techniques, emergency protocols, and updates on regulatory changes. This should start with an initial orientation and continue with regular refreshers.

Training should also include practical exercises, written tests, and simulations to reinforce knowledge. For example, staff can demonstrate their understanding of hygiene protocols by correctly following gowning procedures or responding to simulated emergencies.

To maintain high standards, conduct regular skill assessments. These can include observing staff during tasks, hands-on demonstrations, and written evaluations on standard operating procedures (SOPs) and regulatory requirements.

Thoroughly document all training and assessments. If gaps in performance are identified, address them immediately with focused remedial sessions. Hands-on practice, guided by experienced mentors, tends to be more effective than traditional classroom learning for boosting compliance.

With a skilled and prepared team, your facility will be well-positioned for the certification process.

7. Complete Certification Process

Once you've set up the required design, construction, and monitoring systems, it's time to move on to the final step: certification.

Conduct a Self-Inspection

Before scheduling the official certification, take time to review key areas:

• Environmental Controls and Monitoring: Check that temperature, humidity, air changes, and monitoring systems align with USP standards.

• Documentation: Confirm all maintenance records, training logs, and standard operating procedures (SOPs) are up-to-date.

• Staff Compliance: Verify recent training records and ensure all team members are following protocols correctly.

Schedule the Official Inspection

The official inspection process typically includes the following phases:

"Certification reports must be reviewed by the designated person(s) to assure that all requirements have been met." - Eagle Cleanroom Certification Team

For 503B facilities, stricter cGMP standards apply, including tighter environmental controls. Certification must be renewed every six months or after any significant changes to the classified area.

If any issues come up during the inspection, reach out to clean room specialists for advice on fixing them. Once certification is complete, your clean room will be ready for safe, compliant operations, setting you up for long-term success.

Conclusion

Achieving clean room certification requires careful execution at every stage, from planning to ongoing upkeep. This process is a key step to ensure patient safety and meet regulatory demands. It calls for precision during the initial setup and a long-term commitment to maintaining the required standards.

Maintaining certification hinges on three main areas:

"Certification that the cleanroom is operating within the ranges set forth is the final step before occupancy and use of the pharmacy." - CETA Guidelines

Routine audits and monitoring are essential for staying compliant with USP <797> and <800> standards. A structured audit program should cover every part of medication preparation and dispensing, with clear steps to fix any issues that arise.

FAQs

What are the requirements for a clean room in pharma?

Pharmaceutical clean rooms must adhere to USP <797> and <800> standards, which regulate factors like temperature, humidity, air changes, and particle levels to ensure sterility and product safety. These standards are critical for maintaining ISO Class 7 conditions and safeguarding product quality.

"The key components that need to be certified include Primary Engineering Controls (PEC), such as fume hoods, and Secondary Engineering Controls (SEC), which encompass the clean room space housing the PEC"

Key elements of a compliant clean room include:

• HEPA filters and laminar airflow systems for air quality control

• Real-time monitoring to track environmental conditions

• Unidirectional workflows to reduce contamination risks

Clean rooms must meet ISO Class 7 requirements, as specified in USP <797> and <800>. Certification is required every six months, following CETA guidelines, to confirm that both primary and secondary engineering controls comply with these standards.

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