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NOBBIO Consulting LLC

Tel
:
043-286-1557
Mail
:
tateishinbo@nobbio.net

Consultation to support Product Development and Commercial Manufacturing

The following is an example of our consultation service to GXP activities in product development and commercial manufacturing of medical supplies such as small molecule drug products, biopharmaceuticals and/or regenerative medical products. The services described here can be extended, in principle, also to medical device and cosmetics.

Consulting Overview

Non (pre) clinical stage (drug research phase)

  • Planning of R&D strategy (road mapping)
  • Planning of development strategy scenario and progress check
  • Planning of development strategy of product candidate (establishment of proof of concept)
  • GMP management for investigational medicinal product (clinical trial material) including control of the contract manufactures and/or test facilities
  • Regulatory compliance and Quality Assurance of investigational medicinal product, including timely updates of the clinical trial applications (IND and IMPD)
    • Planning of an initial specification for raw materials/excipients, intermediates and final product
    • Maintenance and control management of a manufacturing and testing records (log book)
    • Planning of record maintenance system for manufacturing process, analytical methods and specifications under assurance of its integrity
    • Analytical method validation (to the extent required under IND and IMPD)
    • Stability testing (to the extent required under IND and IMPD)

Clinical stage (Chemistry, Manufacturing and Control (CMC) and clinical trial application)

Early Clinical Phase
  • Quality Assurance of investigational Medical Product (compliant to GMP and regulatory dossier)
    • Documentation of manufacturing and testing procedures (Product Specification File and SOP)
    • Qualification of facilities and equipment
    • Registration of specifications for raw materials (including packaging material) and final product
    • Procedure for product release approval (cooperation with QP in Europe)
    • Validation of manufacturing process (to the extent required under IND and IMPD)
    • Aseptic process assurance (validation)
    • Cleaning validation/verification (to the extent required under IND and IMPD)
    • Deviation management and change control
    • Label management (to the extent required under IND and IMPD)
  • Updates of clinical trial applications/stage shift (IND, IMPD and investigator’s brochure)
  • Qualification and contracts with suppliers for raw materials, container/closure etc., contract manufactures, and product storage and distribution agents
  • Consultation meeting with authorities (development and/or approval strategy, documentation and quality issues)
Late Clinical Phase
  • Establishment of manufacturing and quality control strategy for commercial products (NDA/BLA preparations)
    • Establishment of a commercial manufacturing process
    • Qualification of facilities and equipment used for commercial manufacturing
    • Process validation and analytical method validation for commercial manufacturing
    • Completion of cleaning validations and environmental monitoring for commercial manufacturing
    • Maintenance and control of manufacturing and testing records (with data integrity)
    • Other GMP/GDP relating matters
      • Risk management
      • Employee trainings and GMP education
      • Qualification and contracting with domestic or overseas contract manufacturers and/or testing organizations (CDMO)
      • Qualification and business and contracting with venders or suppliers of raw material, labelling materials, container/closure etc., and product storage and transportation agents
      • CSV compliance (including data integrity)
      • Supply chain management including validated transportation for clinical and/or commercial products (GDP compliance)
  • Consultation meeting with the regulatory authority (approval strategy, documentation and quality issues)

Filing of commercial license and Pre-approval inspection

Handing of Q&A from a regulatory authority pertinent to commercial license application
Preparation of Marketing and Manufacturing license Application (NDA/BLA, CTD and DMF)
Consultation meeting with regulatory authority (approval strategy, documentation and quality issues)
Filing of Marketing and/or Manufacturing license registration application
Foreign Manufacturer Accreditation application and appointment of domestic agent
Readiness for Inspection (Pre-Approval Inspection) by a domestic and overseas authority
Mock Inspection and Inspection readiness management

Commercial Manufacturing Stage

Periodical audit
Management and supervise of domestic and overseas raw material suppliers (audit)
Management and supervise of domestic and overseas contract manufacturers and/or testing organizations (audit)
Readiness for audit by a marketing license holder (mock inspection and GMP education and training)
Inspection by authority
Hosting and management for Inspection by domestic and/or overseas authorities (mock inspection and GMP training and education)

Regenerative medicine product, nucleic acid medical supplies and gene therapy

Development of a regenerative medicinal product, nucleic acid medical supplies and a gene therapy will require early establishment of manufacturing and quality controls securing the safety and efficacy. This is because accelerated review and support by authority for filing and approval for commercial license can be expected if an authority admits the potential for medical merit of the product. Therefore, when compared to other medicinal products, the special strategy is required for planning and evidence proof for product quality in early development stage and will play an important role for accelerated approval purpose. Evaluation for product quality control is required in accordance with the product characteristics and identification of any product associated problems and GMP (GCTP) issues are key for development management.

  • Establishment of effective Quality Management System for GCTP facilities
  • Establishment of aseptic assurance (sterilization assurance of facilities and equipment)
  • Compliant to “Biological Raw Material Standard” regulation (ICH compliance)
  • Optimization and validation of manufacturing process
  • Validation of analytical method for in-process control, characterization analysis and a release testing (ICH compliance)
  • Valid documentation (system) of various reports and SOPs, etc. (data integrity)
  • Consultation meeting with regulatory authorities (approval strategy, documentation and quality issues)
  • Communication (Q&A) with authorities in regard to Marketing and Manufacturing License application

Moreover, the services are available to support the investigations for safety and efficacy of the product candidates that will be required under regulation in the gene therapy field, such as regulatory acceptable vectors and raw materials with (higher) safety.