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Rapid Sterility Testing Regulations

POSTED BY Rapid Micro Biosystems | 9 minute read

 

Navigating Regulation and Validation for Rapid Sterility Testing

In the world of pharmaceutical manufacturing, sterility testing is an essential regulatory process to ensure that your products are free from microbial contamination. Compared with compendial testing methods, rapid microbiology methods (RMM) offer significant advantages in speed and accuracy. Platforms such as Growth Direct® Rapid Sterility detect contamination events earlier to support timely interventions, and quickly initiate root cause investigations to begin mitigation.

Despite these benefits, many manufacturers remain reluctant to upgrade their sterility testing system due to perceived regulatory challenges and lengthy validation processes. The reality, however, is that regulatory bodies, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), encourage the adoption of RMM technology for sterility testing and have set initiatives in place to simplify the validation process.

If you’re currently evaluating whether to make the switch to rapid sterility testing, read on!

Explore the benefits of rapid sterility testing

Understanding sterility testing regulations

Many sterile manufacturers have concerns or doubts about the level of regulatory acceptance for RMM, and this misconception is one of the major barriers to the adoption of rapid technologies for sterility testing.

The truth is, regulatory agencies worldwide, including the FDA, EMA, and others, have recognized the industry’s need for rapid methods and promoted their implementation and use through various documents and guidelines. These include the FDA's Process Analytical Technology (PAT) initiative, cGMP guidelines, and specific guidelines like the FDA aseptic processing guidance.

The major regulatory bodies have universally highlighted the benefits of RMM, freeing the industry from any hesitation to embracing advanced automation technologies – citing their ability to yield accurate and reliable test results in less time and with less operator intervention versus compendial methods.

Rapid sterility testing validation

The validation process for implementing RMM requires you to demonstrate that the new method is suitable for your intended purpose by demonstrating its specificity, limit of detection, robustness, accuracy, and reproducibility.

The FDA recommends using documents USP 1223 and PDA Technical Report 33 as starting points for validation and expects scientifically sound and defendable validation strategies. If your rapid sterility testing technology is novel, there’s nothing like a robust body of peer-reviewed journals that exhibit your technology to help convince FDA reviewers that it’s scientifically sound.

There are several critical considerations for developing a robust validation strategy for rapid microbiological methods (RMM):

Where will you perform validation testing?

Outsourcing to contract laboratories can be appealing for companies with limited internal resources or those seeking to expedite the validation process. However, this can limit the knowledge and skills gained by your internal team.

Instead, we recommend conducting your validation testing in-house. This gives you greater control over the process and ensures that your staff gain valuable hands-on experience with the new technology.

By partnering with Rapid Micro Biosystems® (RMB), your staff can benefit from our comprehensive validation and onboarding support services in the familiar space of your own facility. We provide expert support throughout your validation journey, from documentation to method validation, regulatory assessments, and more.

Utilizing research exemptions

Research exemptions give you the opportunity to optimize your methodology through exploratory studies and pilot tests prior to any validation assessments or implementation of rapid microbial testing systems. These studies have the added value of generating actionable data while gaining platform experience away from the full regulatory scrutiny and performance pressures of official validation assessments.

Comparability protocol

The comparability protocol is a written agreement with the FDA that includes information on test methods, acceptance criteria, and more. Once approved, as long as the company adheres to the outlined steps and meets the defined criteria, the FDA agrees to accept the new method.

This strategy is advantageous for companies with a large product portfolio, as it avoids the need for separate validation of each product, saving time and resources.

To maximize your chances of approval, conduct thorough feasibility/development studies before finalizing your protocol. And if you engage with the regulatory bodies early in the process, you can discuss and address any potential concerns or requirements. Being proactive helps build a collaborative relationship and ensures that the protocol aligns with their expectations.

Instrument Validation

Instrument validation ensures the proper functioning and installation of the equipment. It involves the following stages:

  • Instrument Qualification (IQ): Verifies the equipment is installed correctly and meets manufacturer specifications.
  • Operational Qualification (OQ): Confirms the system operates correctly under specified conditions.
  • Performance Qualification (PQ): Validates the system's performance under actual production conditions.

When you partner with RMB, all instrument validation steps are performed upon installation of the Growth Direct® System as part of a comprehensive validation package.

Method validation

Method validation focuses on demonstrating the reliability, suitability, and equivalence of the new rapid microbiological method for sterility testing. This process includes the following checkpoints:

  • Time to Results (TTR): Measures the time required to detect microbial growth and ensures the rapid method reduces overall testing time compared to compendial methods.
  • Method Qualification (MQ): Confirms the alternate method's Limit of Detection (LOD) and equivalence to traditional compendial methods using statistical analysis of low CFU levels and comparisons with the current sterility testing approach.
  • Method Suitability Testing (MST): Verifies the method’s compatibility with the specific products being tested, ensuring no interference with the detection technology or false results.

Each phase of method validation ensures the rapid sterility testing method is scientifically sound, reproducible, and suitable for regulatory approval​.

Read more on how RMB partners with customers for method validation support

A smoother road towards regulatory acceptance

Make your validation journey a smooth transition by working with a partner with proven technology and experience. At RMB, we have developed a validation pathway that simplifies the adaptation from compendial methods to RMM:

  • Comprehensive support: RMB provides end-to-end support, from initial feasibility studies to full-scale deployment. No matter the size of your operations, our team of experts assist with every step of the validation process. Read about Lonza’s customer journey working with RMB: Building a Digitalized End-to-End Process for Environmental Monitoring.
  • Proven technology: Our Growth Direct® system has been validated and proven in various applications, including environmental monitoring and bioburden testing. The robustness and accuracy of the technology have been demonstrated through an extensive body of peer-reviewed research, providing a solid foundation for sterility testing validation.

By following RMB’s tried and tested validation pathways, you can transition to RMM with confidence.