All posts by admin

Combination Products: Development and CMC Requirements for Registration of Drug Delivery Devices and Prefilled Systems

  • Commonly used drug delivery devices – technologies, design, materials, and performance characteristics.
  • Selecting materials and manufacturing components for drug delivery devices.
  • How to interpret and comply with current FDA regulatory requirements for combination products; what combination product regulations, guidance and standards do and do not exist, or apply; how to manage gaps in the regulatory framework.
  • How to comply FDA’s Final Rule and guidance: Current Good Manufacturing Practice Requirements for Combination Products; requirements for pharmaceutical and medical device companies, contract manufacturers and contract manufacturers and constituent part and component part manufacturers.
  • How to report post-approval design and manufacturing changes.
  • How to conduct “bridging studies” to support presentation switches (e.g., prefilled syringe to autoinjector).
  • Compendial and harmonized standards for drug delivery devices and their materials and components.
  • How to interpret and conform to FDA draft and final guidance documents, including Technical Considerations for Pen, Jet, and Related Injectors Used with Drugs and Biological products, and Container Closure Systems for Packaging Human Drugs and Biologics.
  • How to assess the biocompatibility of materials used to manufacture of drug delivery devices components; how to evaluate chemical and toxicological reports from suppliers.
  • Current guidance and standards related to extractables and leachables; industry “best practices”; efficient and compliant extractable and leachable study work flows

Combination Products: Human Factors-Usability, Quality Systems and Design Controls for Drug Delivery Devices

  • Building, optimizing and applying human factors and usability engineering processes
  • Understanding human factors and usability expectations of three different FDA centers.
  • Establishing reasonable expectations with reviewers so that review meetings and submissions have successful outcomes.
  • Utilizing human factors and usability studies to identify potential use errors and their mitigations when developing a new device or modifying an existing device.
  • Writing a Human Factors Validation protocol for human factors and usability engineering. When it’s necessary to submit it for review prior to execution.
  • The most significant human factors and usability deficiencies cited FDA over the past decade.
  • The most common reasons why companies and regulators differ over human factors/usability issues.
  • Applying human factors and usability engineering principles to legacy products.
  • Using human factors/usability engineering in evaluating potential device suppliers.
  • The key human factors/usability questions to ask device vendors.
  • How to comply with current quality systems regulations, directives, guidance and standards for device-containing combination products and their applicability to pharmaceutical and medical device developers, contract manufacturers and constituent part and component part manufacturers.
  • Interpretation of current quality system guidance, industry best compliance practices, recent inspectional experience and FDA enforcement action for device containing combination products.
  • How to implement and utilize design controls, including design verification and validation testing, during development of device containing combination products.
  • What to do about a Design History File for a legacy product.
  • Including compliance information in marketing applications.

Combination Products: Understanding FDA Requirements for the Development, Registration and Marketing of Prefilled Syringes, Drug Delivery Devices and Systems

  • Drug and biologic delivery technologies
  • What combination product regulations, guidance and standards do and do not exist, how to interpret, comply or conform to them and how to manage gaps in the regulatory framework
  • How to comply with the final rule on combination product good manufacturing practices and its impact on pharmaceutical companies, contract manufacturers and device constituent part and component part manufacturers
  • How to interpret and conform to recommendations in FDA-OCP guidance on technical considerations for pen, jet, and related injectors used with drugs and biological products
  • How to structure and format combination product CTD applications and labeling
  • How to interpret and apply the recommendations of FDA human factors related guidance documents
  • How and why to implement design controls and human factors usability/design validation studies and current trends in utilizing these tools in pharmaceutical development
  • How to report post-approval design and manufacturing changes to marketing applications and how and when to switch combination product presentations (e.g., vial to prefilled syringe, prefilled syringe to autoinjector); how to “bridge” presentations
  • Registration and Listing requirements for combination products

Combination Products: Establishing and Utilizing an Integrated Approach to Developing Drug/Biologic Containing Medical Devices and Delivery Systems

  • Final rule and guidance on combination product good manufacturing practice; Design Control and drug cGMP requirements impacting pharmaceutical and medical device manufacturers, contract manufacturers and combination product constituent part and component part manufacturers.
  • Integration of device Design Control and drug cGMP requirements into existing pharmaceutical and medical device development practices and quality systems
  • How to apply risk assessment and management processes in support of compliance with the new combination product post-marketing safety reporting rule.
  • Key governance and management systems practices intended to effectively integrate product development and a design review process.
  • How pharmaceutical and medical device voice of the customer practices can be integrated into user requirement/design inputs and drive the development process.
  • Drug and device characteristics important in design verification planning to provide objective evidence that design outputs satisfy design inputs.
  • Utilizing human factors/usability engineering in device, drug and combination product design development.
  • Use of drug and device clinical and human factors studies and device benchtop testing to satisfy design validation requirements.
  • How to integrate project management and design and development planning to effectively define drug and device development activities, needed resources, interfaces, responsibilities, and activities.
  • Application of design transfer practices to ensure device and pharmaceutical requirements are effectively integrated into existing pharmaceutical manufacturing process transfer practices.
  • The use and benefits of a Device Master Record in satisfying design output requirements.
  • How to manage design changes and modifying existing change control systems to comply with design control requirements.
  • Implementation of effective pre- and post-market Design History File practices to integrate drug, device and the combination product design evolution.
  • Use of a Quality and Compliance Plan to identify procedures and resources for combination product development and plan implementation of quality system elements into medical device or pharmaceutical development organizations.
  • Compliance and Enforcement – Current FDA’s approach to evaluating the Design Controls process; how to prepare for a combination product design control inspection.

Combination Products: A Structured Approach to Complying with Post-marketing Safety Reporting and Good Manufacturing Practices

  • How to comply with FDA’s Final Rule on Post-marketing Safety Reporting for Combination Products and its impact on pharmaceutical and medical device companies, and constituent part manufacturers; what to consider when designing a post-marketing safety reporting system
  • How to comply with FDA’s Final Rule and Guidance on Combination Product Good Manufacturing Practice and its impact on pharmaceutical and medical device companies, contract manufacturers and constituent part and component part manufacturers; industry best compliance practices and FDA enforcement
  • Required actions resulting from the interplay between safety reporting, good manufacturing practices and corrective action requirements
  • How to improve current complaint management system which may be inadequate for complaint device failure/malfunction investigations
  • Integration of device design controls and drug cGMP requirements into existing pharmaceutical and medical device development practices and quality systems
  • How to utilize design controls, risk management and human factors engineering in medical device and pharmaceutical environments, to legacy combination products and combination products currently in development to improve design and comply with regulations

Combination Product Compliance

  • How to comply with and interpret FDA’s Final Rule: Post-marketing Safety Reporting for Combination Products.
  • What combination product regulations, guidance and standards do and do not exist, how to interpret, comply or conform to them and how to manage gaps in the regulatory framework.
  • Current FDA regulatory requirements and recommendations for combination products and industry best compliance practices.
  • Final Rule and Draft Guidance on Combination Product Good Manufacturing Practices; impact on pharmaceutical and medical device companies, contract manufacturers and constituent part and component part manufacturers; industry best compliance practices; FDA enforcement action.
  • How to implement design controls for legacy combination products and products in development.
  • Design verification, design validation and human factors usability studies in combination product development; current trends and industry best practices.
  • Reporting of post-approval design and manufacturing changes to combination product applications; presentation switches, bridging.
  • CMC requirements including stability studies, extractables and leachables, compendial requirements and standards.
  • Format and content of investigational exemption applications and marketing applications; eCTD, NDA/BLA format for device containing combination products.
  • Combination product breaking news and hot topics.

Artificial organ quality system

A start-up company developing a tissue product used in organ replacement asked for Chimera’s help in establishing a quality system that was compliant with CGMP, QSR and Good Tissue Practice requirements. Chimera worked with the QA department in structuring the quality system and drafting quality policy and procedures. Chimera also recommended that since the shipping container contained functional elements its design should also be developed under a medical device design control system.

Biologic-device bridging strategy

A biotech manufacturer sought Chimera’s advice on bridging strategy design to achieve approval of a pre-filled cartridge-injection pen following the approval of a presentation containing a similar but not identical drug formulation. Prior clinical studies had been conducted with vialed product which utilized drug-contacting materials that were different from those to be used in the manufacture of the cartridge-injection pen. Chimera assisted the manufacturer in the development of a Type C Meeting briefing document which was submitted to CDER division responsible for the regulation of the combination product. Chimera later assisted the manufacturer with interpreting FDAs written responses and planning subsequent development and submission of a sNDA.

Biologic-device delivery device switch

A biotech manufacturer sought to switch a vialed lyophilized injectable biologic to a liquid pre-filled cartridge and pen. There was no significant change in drug-contacting materials. Chimera assisted in planning comparability, compatibility and stability protocols and drafted CMC documentation for the sBLA.

Biologic-device reconstitution and delivery device stability

A biotech manufacturer sought Chimera’s advice on assessing stability parameters of the diluent chamber of a two chamber liquid-dry reconstitution cartridge containing a lyophilized biologic. Chimera provided technical strategy, specifications and a technical approach for the separate determination of the stability of the diluent chamber, the lyo-drug chamber and the reconstituted drug solution.