Solvent Extraction Equipment Cleaning And Sanitization

In industries such as pharmaceuticals, food, and fine chemicals that rely on solvent extraction processes, equipment cleaning and sanitization are more than just "housekeeping." They are directly related to product quality, production safety, and regulatory compliance. Whether preventing cross-contamination between batches of Active Pharmaceutical Ingredients (APIs) or controlling microbial counts in traditional Chinese medicine extraction, a scientific and practical cleaning and sanitization system is key to avoiding quality issues and meeting Good Manufacturing Practice (GMP) and other regulatory requirements. By integrating industry practices and equipment characteristics, we can clarify the key points for cleaning and sanitizing solvent extraction equipment from three perspectives: operational logic, method selection, and effectiveness verification.

The core goal of cleaning solvent extraction equipment is to remove residual materials, solvents, and soil. These residues may react with the next batch of materials and may also become a breeding ground for microbial growth. The entire process should follow the principle of "working from the surface to the interior, removing gross soil first and then fine residues." Avoid creating unreachable corners due to improper operation.

Before cleaning, always disconnect the equipment from the power supply and close all valves. This is especially critical for the valve connecting the solvent storage tank and the extraction tank to prevent solvent leakage and potential safety hazards. Subsequently, completely empty the equipment of any remaining material. Any residual liquid can drain naturally through the drain port. Then, use compressed air or nitrogen to purge the pipelines to ensure there is no liquid accumulation on the inner walls. Any solid debris adhering to the tank walls or impellers (such as traditional Chinese medicine residues or API crystals after extraction) should be scraped off with a soft spatula or a dedicated scraper. Avoid scratching the equipment's interior with hard objects. Scratches on the stainless steel interior can easily harbor soil and debris.

The proper handling of removable parts is crucial. Parts prone to harboring debris, such as filters, pipeline connectors, seals, and impellers, should be disassembled one by one and carefully labeled. For example, label them "Extraction Tank Cover Seal" to avoid confusion during subsequent reassembly. These small parts are often the most challenging to clean. For instance, particles may become lodged in filter pores. If not cleaned separately, they can directly contaminate new material during subsequent use.

Cleaning is not a one-step process; it is carried out in stages. The objectives and methods of each stage differ significantly:

Pre-rinse: Flush the equipment's interior and exterior with room-temperature potable water (or a solvent compatible with residual solvents, such as ethanol). The focus is on removing loose dust, residual solvents, and surface materials. Avoid electrical components and sealed areas, such as motor connections and sensor probes, to prevent water ingress and equipment damage. Vertical pipes can be cleaned with a "counter-current flush," allowing water to flow from bottom to top to reduce residue accumulation on the inner walls.

Deep Cleaning: This is the core step. The key is selecting the appropriate cleaning agent, tailored to the residue type and equipment material. Using an incorrect cleaning agent can corrode the equipment or result in incomplete cleaning. For example:

For organic solvents, grease, and protein residues (such as polysaccharides and alkaloids from traditional Chinese medicine extraction), a 2%-5% alkaline cleaning agent (e.g., sodium hydroxide solution) is often used. Both immersion and recirculating cleaning methods are applicable. Large extraction tanks typically use a circulation system, allowing the cleaning agent to flow through the tank for 2-4 hours, utilizing the alkaline environment to break down organic residue structures.

If inorganic salts or scale residues remain in the equipment (e.g., calcium and magnesium deposits from long-term use of hard water), a 1%-3% acidic cleaning agent (e.g., dilute nitric acid or citric acid solution) should be used. This chemical reaction dissolves the deposits, but the contact time should be controlled, generally not exceeding one hour, to prevent corrosion of the stainless steel interior by the acidic solution.

For special residues (e.g., resins insoluble in acids and alkalis), a dedicated organic solvent cleaner (e.g., isopropyl alcohol) can be used. However, subsequent flushing with ample potable water is essential to prevent solvent residue.

Final Rinse and Drying: After deep cleaning, the equipment must be rinsed with Purified Water. In the pharmaceutical industry, Water for Injection should be used for certain applications. Rinse until the conductivity and pH of the rinse water match those of the Purified Water used, ensuring no residual cleaning agent remains. Dry promptly after rinsing: Small parts can be air-dried, while large equipment (e.g., extraction tanks) should be dried using clean compressed air. Low points in pipelines and valve connectors, where water easily accumulates, require special attention to prevent mold growth in humid environments.

Cleaning removes soil, while sanitization kills microorganisms. Solvent extraction equipment often features enclosed or semi-enclosed structures, particularly in pipelines and storage tanks. Once bacteria, spores, or fungi proliferate, they can directly contaminate the extracted product. For example, Chinese herbal medicine extracts may exceed microbial limits, or APIs may fail to meet standards for objectionable microorganisms. When selecting a sanitization method, it is important to balance antimicrobial efficacy, equipment compatibility, and operational safety.

As it leaves no chemical residue, physical sanitization is the preferred method in the pharmaceutical and food industries. It is particularly suitable for critical equipment that contacts the product directly.

Saturated Steam Sanitization: This is the most commonly used method. It is suitable for equipment that can withstand high temperatures and pressures (e.g., stainless steel extraction tanks and enclosed pipelines). During operation, the equipment must be tightly sealed, and saturated steam at 121°C and 0.1 MPa must be introduced for 20-30 minutes. This method effectively kills almost all microorganisms, including spores. Care must be taken to remove air from the equipment. Trapped air can cause localized insufficient temperatures, creating "sanitization dead zones" (e.g., tank domes and pipe bends). Vent multiple times through the exhaust valve to ensure steam fills the equipment completely.

Dry Heat Sanitization: Suitable for components that are moisture-sensitive and heat-stable, such as glass sight glasses, metal sampling spoons, and certain filter cartridges. The components are placed in a dry heat oven at 160-180°C for 2-4 hours. The high temperature denatures microbial proteins. However, dry heat has a slow heating rate, high energy consumption, and is not suitable for plastic parts (which may deform).

Ultraviolet (UV) Disinfection: Primarily used for auxiliary disinfection of equipment surfaces (e.g., tank openings, operating platforms) and small tools. The UV lamp should be positioned no more than 1 meter from the surface to be disinfected and should irradiate for 30-60 minutes. Disinfection is achieved by destroying microbial DNA. However, UV light has poor penetrating power and cannot eliminate microorganisms inside equipment or in shadowed areas, so it can only serve as a "supplemental surface disinfection" method.

If the equipment cannot withstand high temperatures (e.g., extraction tanks with precision sensors) or requires rapid sanitization, chemical methods can be used. However, disinfectant residue must be strictly controlled:

Immersion or Wipe Disinfection: Removable components (e.g., seals, filters) can be immersed in a 75% ethanol solution (suitable for metal and plastic parts) or a 0.1%-0.2% peracetic acid solution (suitable for stainless steel parts) for 15-30 minutes. Equipment surfaces can be wiped with a sterile cloth moistened with disinfectant. Focus on frequently touched areas such as buttons and valve handles. Note that peracetic acid is corrosive; after use, rinse 2-3 times with Purified Water.

Gas Sanitization: Suitable for large, enclosed equipment (e.g., multi-unit extraction systems) or non-dismantlable pipeline systems. Ethylene oxide gas is commonly used. Maintain a specific concentration (800-1200 mg/L) and temperature (30-50°C) in a sealed space for 4-6 hours. However, ethylene oxide is flammable, explosive, and toxic, requiring operation in a dedicated, explosion-proof sanitization chamber. After sanitization, adequate ventilation is required to remove residual gas and avoid harm to personnel and products.

The effectiveness of cleaning and sanitization cannot be judged solely by "visual cleanliness." It must be verified through scientific testing methods to ensure compliance with industry or internal standards. This is key to avoiding "pseudo-cleaning" and "pseudo-sanitization" and is a mandatory check during compliance audits.

First, conduct a visual inspection. The interior and exterior surfaces of the equipment, pipeline connections, and removable parts must be free of visible residue, rust, or water stains. The interior surfaces should be smooth and free of scratches. When inspecting pipelines, an endoscope can be used to check for residue. When inspecting filters, check for unobstructed pores and any blockages.

Next, perform physical testing. The conductivity (generally required to be ≤ 2 µS/cm) and pH (typically 6-8) of the final rinse water can be tested to determine if any cleaning agent residue remains. For equipment subjected to chemical sanitization, surface disinfectant residues should be tested. For example, test strips can be used for residual chlorine from chlorine-based disinfectants; the requirement is typically ≤ 0.1 mg/L.

Microbiological testing is key to evaluating sanitization effectiveness. Sampling should be performed at "critical locations" (e.g., the inner wall of the extraction tank, the discharge port, low points in pipelines):

Surface Sampling: Use the contact plate method (press a sterile culture medium plate onto the equipment surface, sampling an area of 10 cm² per location) or the swab method (use a sterile cotton swab moistened with saline to wipe the surface, then inoculate the swab eluate onto culture medium). After incubation, count the number of colonies. The pharmaceutical industry generally requires a colony count of ≤ 10 CFU/100 cm² at critical locations. Objectionable microorganisms (such as Escherichia coli and Staphylococcus aureus) must not be detected.

Biological Indicator Verification: For equipment sanitized using high-temperature methods, biological indicators (e.g., spores of Geobacillus stearothermophilus) can be placed in potential sanitization dead zones. Perform culture tests after the sanitization cycle. If no growth is observed from the indicator, sanitization is considered effective. If growth occurs, review the sanitization temperature and time, or check for inadequate air removal.

For equipment used for multiple products, test for residues from previous products to avoid cross-contamination. Common methods include:

TOC Testing: Using a Total Organic Carbon analyzer to measure the TOC value on the equipment surface or in the rinse water indirectly reflects the level of organic residues. A TOC value of ≤ 500 µg/L is generally required.

Specific Testing: For specific materials (e.g., active ingredients in traditional Chinese medicines or APIs), use methods such as High-Performance Liquid Chromatography (HPLC) to test for residues. Ensure that the residue level is below the "cleaning validation limit" (often calculated as 1/1000 of the minimum daily dose of the subsequent product or based on health-based exposure limits).

In actual production, cleaning and sanitization of solvent extraction equipment often encounter problems such as "difficult-to-clean dead legs," "residue control challenges," and "high costs." Based on industry experience, the following recommendations are offered:

Incorporate Cleanability in Equipment Design: When procuring new equipment, request manufacturers to optimize the design. Reduce right angles and dead legs (pipeline length-to-diameter ratio should not exceed 3:1), and add cleaning access points and drain valves at low points. Reduce cleaning difficulty at the source.

Develop "Equipment-Specific Cleaning SOPs": Different cleaning and sanitization protocols are required for different types of extraction equipment (e.g., dynamic vs. static extraction tanks) and different residue types (e.g., organic solvents vs. water-soluble materials). Clearly define cleaning agent concentration, contact time, and sanitization parameters; avoid a one-size-fits-all approach.

Strengthen Personnel Training and Record Traceability: Cleaning and sanitization personnel must understand the equipment structure, cleaning agent properties, and safe operating procedures (e.g., wearing acid- and alkali-resistant gloves and safety goggles). Detailed records should be maintained for each cleaning and sanitization event, including time, personnel, methods, and test results. This establishes a traceable management system to facilitate subsequent audits and issue investigation.

Cleaning and sanitization of solvent extraction equipment require a combination of technical and management expertise. Scientific methods must be employed alongside standardized operations and rigorous verification to transform compliance requirements into consistent practices. Only in this way can quality risks be truly eliminated, product safety ensured, and controllable, traceable production processes be achieved.