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