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Process Validation

When the process technology is defined and the manufacturing documentation accurately reflects the developed production steps, the process is ready to move into the Process Qualification Stage.

BioTechLogic has expertise in managing all stages of process validation, and proven experience in presenting the approach, the results, and the conclusions of a successful validation to global regulatory agencies.

Process Validation consists of three critical stages:

  • Stage 1 – Process Design
  • Stage 2 – Process Qualification
  • Stage 3 – Continued Process Verification

BioTechLogic can design the strategy to complete Process Validation in a timely and compliant manner, and effectively manage all activities related to these three phases.

How can BioTechLogic Help?

 

Stage 1:  Process Design

  • Support the development of the Quality Target Product Profile (QTPP) and identification of Critical Quality Attributes (CQAs)
  • Define Process Inputs and Outputs
    • Review production batch records to compile comprehensive list of process parameters
    • Write Parameter Justification Report to define how parameters and ranges were established and controlled throughout development
    • Write Process Development History Reports to appropriately capture process knowledge
  • Determine Potential Critical Operating Parameters, Steps or Raw Materials by Risk Assessment
    • Lead comprehensive, multi-disciplinary process risk assessment to rank potential sources of process variation
    • Write Risk Assessment Reports throughout clinical development (lifecycle approach means risk assessment are being re-visited as process knowledge increases)
  • Experimentally define NOR and PAR for critical parameters using DOE and Statistical Assessment
    • Design an experimental approach that will ensure a risk-based and science-based approach to determining parameter criticality
    • Establish and qualify appropriate scaled-down models
    • Ensure that DOE studies are appropriately designed and interpreted, with experience in JMP, Design-Expert, and MiniTab statistical software
    • Execute Quality by Design
  • Based on DOE studies, establish final list of Critical/Key Operating Parameters
    • Facilitate decision-making with regard to formal PPQ acceptance criteria
    • Implement PDA Technical Report 42 approach for parameter designation to ensure consistency with industry standards
  • Parameter Evaluation / Pre-Qualification Report
    • Write a comprehensive Parameter Evaluation Report as the “roadmap” to all the various risk assessments and process characterization reports
      • Add benefit in that, if formatted appropriately, this document forms the basis for BLA/MAA Section 3.2.S.2.4
  • Execute Support Validation Studies to Define Ranges for Process Definition
    • Design, review, and/or write protocols and reports for process validation support studies, including resin lifetime studies, membrane lifetime studies, media hold studies, process intermediate hold studies, buffer hold studies, process-related impurities removal studies, filter validation, container/closure validation, etc.
  • Final Process Control Strategy
    • Write a Process Control Strategy, which is a summary of results from the validation support studies and the process characterization work, and provides the critical link between Stages 1 and 2 of Process Validation
  • Define the Process by Finalizing the Batch Record
    • Ensure that the highest quality batch records are carried forward into Process Performance Qualification (Stage 2) based on extensive scientific/process and quality/regulatory experience

Stage 2:  Process Qualification

  • Create Continued Process Verification strategy
    • Guide a multi-disciplinary team through a risk-based and science-based approach to a step-down plan from PPQ sampling and testing strategy
    • Write a CPV Master Plan/Strategy Document
    • Guide manufacturers in implementation of sponsor’s CPV plan
    • Review manufacturers quality systems to ensure appropriate mechanisms are in place to feed appropriate data/information from systems into overall CPV assessments
  • Compile and assess CPV data after each batch
    • Ensure appropriate systems are in place at manufacturer to compile CPV data/information and to communicate the “validated state” across the organization in a timely manner
  • Maintain/Assess Qualified Process via appropriate CAPA and Change Control
    • Review change control documentation to ensure compliance with regulatory expectations
  • Utilities, Facility, Equipment, Components, Raw Materials and Analytical Readiness
    • Ensure that appropriate risk assessments and qualifications are in place for production facilities, utilities, and equipment
    • Ensure that appropriate raw materials and components risk assessments and vendor qualifications have been performed
    • Ensure that appropriate analytical method qualification has occurred prior to Stage 2 Validation
  • Write Process Performance Qualification Protocol(s)
    • Ensure that appropriate assessment of historical data (both small-scale and production-scale) has been completed to define the appropriate number of PPQ batches to define in PPQ protocol(s)
    • Ensure that PPQ approach is appropriately connected back to process knowledge gleaned during Stage 1 Validation
  • Execute Process Performance Qualification Batches
    • Provide Person-in-Plant support prior to, and/or during, PPQ campaign to facilitate communication between client and manufacturing facility and to ensure immediate oversight of production and to provide troubleshooting capabilities
  • Write Process Performance Qualification Report(s)

Stage 3:  Continued Process Verification

  • Create Continued Process Verification strategy
    • Guide a multi-disciplinary team through a risk-based and science-based approach to a step-down plan from PPQ sampling and testing strategy
    • Write a CPV Master Plan/Strategy Document
    • Guide manufacturers in implementation of sponsor’s CPV plan
    • Review manufacturers quality systems to ensure appropriate mechanisms are in place to feed appropriate data/information from systems into overall CPV assessment
  • Compile and assess CPV data after each batch
    • Ensure appropriate systems are in place at manufacturer to compile CPV data/information and to communicate the “validated state” across the organization in a timely manner.
  • Maintain/Assess Qualified Process via appropriate CAPA and Change Control
    • Review change control documentation to ensure compliance with regulatory expectations