AAMI TIR 48 pdf free download

AAMI TIR 48 pdf free download.Quality Management System (QMS) Recommendations on the Application of the U.S. FDA’s CGMP Final Rule on Combination Products.
2.1.3 Examples of single-entity combination products (21 CFR 3.2.(e)(1) include:
• a monoclonal antibody combined with a therapeutic drug
• a device that is coated or impregnated with a drug or biologic — for example:
– Drug-eluting stent; pacing lead with steroid-coated tip; catheter with antimicrobial coating; condom with spermicide
– Orthopedic implants containing antimicrobials
• Prefilled devices, including syringes, insulin injector pens, metered dose inhalers, transdermal patches
2.1.4 Examples of products that can comprise cross-labeled combination products (21 CFR
3.2(e)((3) and (4) include:
• a light-activated drug and activating light source
• an iontophoretic drug delivery patch and controller
2.2 CGMP requirements
2.2.1 When constituent parts of a combination product are manufactured separately, as may be the case for cross-labeled combination products, the constituent parts are subject only to the CGMP regulations applicable to that type of constituent part (e.g., drug or device). For ‘single-entity’ and ‘co-packaged’ combination products, the Rule describes a streamlined regulatory framework for demonstrating compliance with CGMP requirements. Manufacturers may demonstrate compliance with drug CGMPs and Quality System (QS) Regulation by either:
• Fully implementing the device QS Regulation (21 CFR Part 820) and the Drug CGMPs (21 CFR Part 21 1) or
• Following the Streamlined Approach:
— Fully implementing the device QS Regulation and also provisions of 21 CFR Part 211 specified in the Rule, or
– Fully implementing the drug CGMPs and also provisions of Part 820 specified in the Rule
2.2.2 Where multiple facilities bear responsibility for different aspects of the manufacturing process, each facility is responsible for the CGMP requirements applicable to the activities performed at its facility. The combination product marketing authorization holder3 is responsible for ensuring compliance with all aspects of CGMP requirements applicable to the entire manufacturing process and across all facilities.
2.2.3 Manufacturers may opt for the full implementation approach or for either of the Streamlined Approaches. Regardless of the CGMP approach selected, manufacturers of combination products that include a biologic or an HCTIP must comply with biological product CGMPs and CGTPs for Ha/Ps, respectively.
3 Considerations in transitioning to ‘Streamlined Approach’
3.1 Overview of considerations
3.1.1 With the release of the Rule, the FDA codified the ‘Streamlined Approach’ for compliance with combination product CGMPs. Tables 3.2 and 3.3 highlight questions (technical or practical) that may arise when transitioning from manufacture of a device, drug, or biological product to manufacture of a combination product. The “considerations’ address particular topics for combination products relating to each specific CGMP requirement (“element”).
3.1.2 The considerations are not intended to be comprehensive, and the element discussed may focus on specific aspects of a broader issue. Users of this AAMI TIR should refer to relevant CGMP regulations, guidance, and standards for additional information on how to address the identified elements. Guidance documents and recognized standards related to specific aspects of CGMPS can be found on the FDA website through the Office of Combination Products home page and the home pages for the Center for Biological Products Evaluation and Research, Center for Drug Evaluation and Research, and Center for Devices and Radiological Health. Guidance documents of international organizations focusing on regulatory harmonization and convergence in which the FDA participates (e.g., International Medical Device Regulators Forum [IMDRF] and International Conference on Harmonisation [ICH]) should also be reviewed. See examples of relevant guidance and references in the Bibliography to this AAMI Technical Information Report.AAMI TIR 48 pdf download.