With an accomplished staff that boasts decades of biopharmaceutical industry experience, BioTechLogic, Inc. has helped numerous clients bring biopharmaceutical products to market. These case studies offer a glance at some recent successes—and how we worked as a team with our clients to achieve them.
BioTechLogic performed a technology evaluation for a drug substance manufacturer located in Basel, Switzerland to evaluate the commercial process for the U.S. market. The original submission filed with the FDA was being held up, and had numerous observations linked to the manufacturing process. BioTechLogic performed an assessment of the development work, the technology and the manufacturing process, and a comprehensive plan was put together to address the observations. The plans included: additional characterization at in-process steps, the addition of process controls, processing changes and analytical method changes.
TECHNOLOGY AND FACILITY EVALUATION
BioTechLogic performed a technology and facility evaluation for a potential drug product manufacturer located in Bombay, India to produce clinical supplies for studies being conducted in the U.S. and Canada. The manufacturer had the formulation technology in-house, and would therefore be able to meet the client’s aggressive timelines. BioTechLogic performed an assessment of the facility, equipment, and process, as well as an assessment of the qualification/validation status of each. A remediation plan and associated Project Plan and Schedule were then assembled. The major areas of remediation included: environmental monitoring, gowning, operations in classified areas, media fill procedures and process validation.
PAI READINESS EFFORT
A client was preparing for the validation, submission and pre-approval inspection of a facility, process and product estimated to be a “blockbuster” drug, if approved. As part of the PAI readiness effort, the product sponsor hosted several “Mock PAIs” that resulted in significant observations spanning the process, product and facility. BioTechLogic developed a risk-ranking tool that categorized each observation, ranked them by severity and probability of occurrence, and developed the plan for remediation.
The outcome of the risk ranking exercise yielded five major areas for immediate remediation: Technical Development (Synthesis, PEGylation, Purification), Environmental Monitoring and Controls, CAPA and Open Investigations, Critical Facility and Utility Systems, and QC Lab Practices. BioTechLogic developed the remediation plan involving multi-disciplinary teams and various contract companies to establish the deliverables and drive the process to completion.
TECHNOLOGY AND FACILITY EVALUATION
BioTechLogic performed a technology and facility evaluation for a drug substance manufacturer located in Bangalore, India to produce initial clinical and commercial supplies for the U.S. and Canada. The manufacturer was already producing drug substance for distribution in local markets. BioTechLogic performed an assessment of the facility, equipment and process, as well as an assessment of the qualification/validation status of each. A remediation plan and associated Project Plan and Schedule were then assembled. The major areas of remediation included: raw material and cell bank, process parameters and controls, process validation, analytical characterization, equipment qualification, utility qualification and process flow.
INTERNATIONAL INSPECTION READINESS PROGRAM
BioTechLogic developed and implemented an international inspection readiness program and Bio-validation strategy for a Global Supply Chain that supported the approval of Somavert® by the FDA (CDER) in March 2003 and by EMEA in May 2003, followed by approvals in Canada and Japan. Supply chain sites included a new drug substance manufacturing site (no prior FDA or EMEA experience), a new analytical and stability lab (no prior FDA or EMEA experience), a drug product manufacturing site with extensive experience with FDA and EMEA, and several additional support analytical laboratories with FDA experience.
A client was preparing for the BLA submission of a product estimated to have a significant edge over similar products already on the market, if approved. BioTechLogic prepared the CMC sections (Module 3 and Module 2.3, Quality Overall Summary) for the initial indication ahead of the target submission date. FDA review of the CMC sections resulted in only minor questions. As a result, the product sponsor contracted BioTechLogic to write the CMC sections for subsequent indications for submission in both the U.S. and E.U. Additionally, BioTechLogic developed the strategy and plan for the subsequent submissions and provided project management leadership for the various cross-functional teams charged with delivering the BLA/MAA.
A client was preparing for a BLA and MAA submission of an Adjuvant, Drug Substance (Antigen) and Drug Product and needed support with Process Validation and on-site commercialization readiness for the process validation, submission and pre-license inspection. BioTechLogic directed the approach for development activities, process validation, support validations, and readiness for process validation and commercialization.
BioTechLogic provided On-Site Senior Quality and Manufacturing/Technology Management at the client’s Ex-US facility. We were contracted to direct development, process validation and commercialization readiness activities. This included directing the Quality (GMP remediation activities, approval of all “Process Validation – (Stage 1,2, and 3 related documents and led the team in the QRA) and Manufacturing/Technology organizations in the development of all the plans and protocols needed to support the three stages of process validation. This project included, but was not limited to the following:
Stage 1: Process Design
- Process Trending Report: Justification of ranges
- FMEA (Operating Parameters): Identification of potential critical process parameters.
- DOE Studies
- Pre-Qualification Report (summarize DOE study findings and draw conclusion on critical process parameters)
- Quality Risk Assessment: FMEA to reduce variability from other sources of variability).
Stage 2: Process Qualification
- Equipment, Facility and Utility Qualifications
- Vendor Qualification (Raw Material testing requirements prior to process validation).
- Preparation of Upstream and Downstream Process Validation Protocols
- Preparation of PV Summary Reports
Stage 3: Continued Process Verification
- CPV Protocol
BioTechLogic also prepared Module 2.3 and Module 3 in the CTD format for use in preparation of the BLA and MAA. The client received no questions from FDA or EMA on the antigen process validation approach or program.