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Sterilization For EN 285, 21 CFR, and cGMP Requirements

For years, Beta Star has been providing high-level pharmaceutical steam sterilizing autoclaves to pharmaceutical facilities. Having a reliable provider of sterilization equipment for these types of laboratories, with the documentation to back it up, is paramount to the success of our customers’ applications for new drugs, processing of drugs, and proper sterilization of finished drugs before distribution. Our current customers in these environments have trusted Beta Star to provide the necessary documentation to meet stringent requirements including the European guidelines defined in EN 285:2015, Title 21 of the FDA’s Code of Federal Regulations (CFR), and adherence to cGMP guidelines.

Sterilization and EN 285:2015

EN 285 is required for companies and organizations that are currently exporting or plan to export sterile products to the European Union (EU). Though developed in Britain, these guidelines govern sterilization requirements across the EU, specifically related to the quality of the steam being utilized in the steam sterilization of critical equipment and pharmaceutical drugs. In steam sterilization, the absence of non-condensable material (air or other non-sterilants) is vital to ensure complete load sterility as non-condensable material insulates pathogens from sterilization environments. Measuring the quality and thoroughness of steam penetration is carefully conducted, when required, in Beta Star sterilizers through a series of equipment upgrades:

  • EN 285 steam test elbow and ports
  • Air detector port, metering device, and alarm
  • Air detector load probe
  • 0.19 psia vacuum stabilization hold alarm
  • And many more

In addition, EN 285 specifies several tests to ensure sterilization for a few laboratory-specific scenarios:

  • Steam dryness
  • Steam superheat degree
  • Steam contamination
  • Hollow load test for long tubes or pipettes
  • Pressure fluctuation min/max thresholds
  • Heat penetration of stacked, condensed material

Title 21 CFR Part 211

Title 21 of the US Food and Drug Administration’s Code of Federal Regulations (CFR) establishes a series of Parts that set the regulatory guidelines for sterilization requirements for pharmaceutical companies at various stages of the drug development and distribution processes. Depending upon your organization’s position in the pharmaceutical industry, you may be required to have sterilization equipment that adheres to the following Parts: 21 CFR Part 211: relates to the guidelines required for finished pharmaceuticals. This Part is often most applicable to Beta Star’s customers, summarized by the FDA below. Though, it is important to note that it is applicable to all equipment, including steam sterilizers.

  • Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.
  • Any substances required for [machine] operation, such as lubricants or coolants, shall not come into contact with components, drug product containers, closures, in-process materials, or drug products so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.
    • Source: FDA website

Through a carefully managed engineering and design process, supported by nearly 40 years of experience in the sterilization industry, Beta Star’s design and manufacturing modifications for pharmaceutical sterilizers ensure that your company’s sterilization processes will be compliant with 21 CFR Part 211.

cGMP Sterilizer Design and Manufacturing

cGMP Certifiable Sterilization

Beta Star works with our customers to provide manufacturing excellence and documentation to facilitate the FDA inspections required to achieve complete cGMP certification for the pharmaceutical manufacturing process. For the drug production process, the most important aspect of the proper cGMP machine design is the design process. Previously mentioned documentation is vital in demonstrating that the machine’s engineering process followed a methodical approach to ensure accurate, repeatable, reliable, and safe control of pharmaceutical equipment which process (sterilize) potentially dangerous media. Incorporating machine redundancies provides coverage for component failure, an important design feature of the Beta Star cGMP sterilizer design.

What Makes Sterilization Equipment cGMP Certifiable

  • Finer mechanical or chemical polishing of process contact surfaces (namely the sterilizer chamber and door(s) surfaces.
  • Upgraded instrumentation with industry-leading temperature and pressure control.
  • Multiple pressure and temperature monitoring systems provide system redundancy.
  • Sanitary vessel and piping connections.
  • Multiple electronic and/or paper recording of continuous process conditions and cycle results to ensure cycle tracking redundancy.
  • Complete Device History Records (DHRs); including physical and chemical test reports for any process contact material and machine design, machine testing documentation, final commissioning documentation.
  • The utilization of specialty metal alloys at various parts of the sterilizer to enhance corrosion resistance properties of the sterilizer, such as 316 stainless steel jackets and/or 2205 Duplex chambers.
  • Completely validated, customer specified control and cycle customization options.
  • Enhanced turnover packages and documented machine records that follow the industry-standard design process.

Turnover Packages and Documented Machine Records

  • User Requirement Specification (URS): customer provided document that describes the essential features of machine functionality.
  • Functional Requirement Specification (FRS): Beta Star’s official documented response to outline the fulfillment of the URS.
  • Performance Qualification (PQ): the tests done on the sterilizer to verify that all FRS parameters are satisfied. PQs are executed through Factory Acceptance Testing (FAT), Site Acceptance Testing (SAT), or both depending on customer needs. Typically PQ’s are designed to verify the most challenging process or control specifications, usually related to load volume and throughput needs.
  • Installation Qualification (IQ): verifies installation and utility specifications are satisfied to ensure accurate, repeatable sterilization performance.
  • Operational Qualification (OQ): a similar test to PQ that is only performed post IQ. The OQ typically repeats any special PQ challenges from the customer specifications for the protection of redundancy. An additional difference between OQ and PQ is that OQ verifies and records the results of the verification for every control selection.
  • Commissioning: the final step in the cGMP validation process that is satisfied when Beta Star and our customer agree that all customer demanded process requirements are satisfied.