Biologics downstream process validation

When it comes to biologics downstream, we all know that the product characteistics relies heavily on the process. Simply put; the product is the process. So, effective biologic or biopharmaceutical downstream process validation contributes significantly to assuring product quality. Biologic downstream processing (DSP) refers to the recovery and purification of a drug substance from natural sources, such as bacterial cells. Its purpose is to isolate, purify and concentrate biotherapeutic material that has been synthesized (upstream processes).

This entails the removal of impurities and contaminants from the upstream processes, including endotoxins, viruses, cell membranes, nucleic acids, proteins, culture media components, process chemicals, and ligands leached from chromatography media. The manufacturing process must be validated through scientifically rigorous and well-documented exercise.


Principle of process validation

Regulatory authorities such as the U.S. FDA now consider process validation as a continuum of activities that encompass the entire product life cycle. As outlined in the guidance document titled “Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach”, validation of biologics downstream process must now take a continual life cycle approach.


Master Validation Plan

The FDA guidance document titled “Process Validation: General Principles and Practices”  defines process validation but the manufacturers are responsible to translate these regulations and guidelines into appropriate validation concepts and schemes. A master validation plan will be important to describe all validation tasks and responsibilities in detail.

A master validation plan should have several major elements as we have outlined below:

  1. Plant Qualification
    1. Installation Qualification (IQ)
    2. Operational Qualification (OQ)
    3. Performance Qualification (PQ)
  2. Process Validation
    1. Validation of the manufacturing process
    2. Cleaning validation
    3. Product change-over procedures


Biologic downstream process validation

As the biopharmaceutical industry continues to advance, the technology utilized in downstream processing has become more advanced and complex. As such, the principles of process validation have been revised by the FDA to reflect some of the goals outlined by the agency’s initiative entitled “Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach.”

At Synergy Bioscience, we will partner with you to design and implement robust and effective validation services for your biopharmaceutical production. Our consulting services will support you with:

1. Prefiltration and Bioburden Reduction Filter

    1. Chemical compatibility
    2. Extractables and patient safety
    3. Bubble point and diffusion determination

2. Single-use assembly

    1. Chemical compatibility
    2. Extracbles/Patient safety/Leachables
    3. Non-permeation test

3. Final Sterilizing Filters and/or Single-use Assembly

    1. Bacterial retention validation
    2. Bubble point/diffusion determination
    3. Chemical compatibility
    4. Extractables/Patient safety/Leachables
    5. Binding study
    6. Particle shedding study


Our consultants and technicians are fully trained and experienced in process validation to ensure you are compliant with the latest regulatory standards.

To discuss how Synergy Bioscience can help you, please contact us