One of the most challenging hurdles for combination products or products sensitive to standard sterilization processes is understanding the requirements for making a claim in the labeling of the product that it is sterile and the regulatory pathway to making such a claim. The Office of Combination Products (OCP) was created in 2002 as a result of the Medical Device User Fee and Modernization Act. The broad assumption in the industry is that if a combination or sensitive product … The regulatory pathways for drug-device combination products can be confusing – generally, companies decide to pursue a drug pathway or a device pathway based on the primary mode of action. There are certain types of combination products where separate marketing applications for the individual constituent parts of the combination product will be reviewed by applicable centers, or there are times a sponsor sees merit in “choosing” this option. Examples of 505 (b) (2)-appropriate combination drug products include: Monoclonal antibody combined with a therapeutic drug (if drug is PMOA) [6], A single marketing application is sufficient for the review of most combination products. For combination products, “Intended mode of action by which part” is checked. The objective is risk reduction by determining product user issues or related hazards with the products at the early design stage. It is estimated that “approximately 1/3 of all medical products under development today are combination products and total sales could reach $115 billion dollars by 2019”. If a product is a combination of Drug A and Biological B but Mode of action is due to Biological B then as per the assigned category (see above categories), the application will be transferred to either CDER or CBER. It is not unusual for sponsors to ask FDA to clarify how HF concepts apply to the development of combination products. Are additional HF studies necessary when the design of the combination product changes? Its main duties include assigning combination product reviews to a center and coordinating timely premarket reviews involving more than one center. ©2019. All written comments should be identified with this document's docket number: FDA-2019-D-0078. There is not always a clear-cut pathway. In each of the first 3 cases, the products are only appropriate for the 505 (b) (2) pathway if the FDA agrees that the Primary Mode of Action (PMOA) of the entire product is the drug. and (6) Class III, drug-device combination products (Table 1). In addition to the use of 3D printers, the advancement of mobile health (mHealth) applications for smart phones and othe… The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. 114-255) (“Cures Act”), substantially amended section 503(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 USC 353(g)), the principal section of the FD&C Act expressly addressing combination products. Device testing includes Human Factors Studies (or aka HF study). Regulatory expertise is critical to sponsors including determination of the best pathway for their specific product. FDA’s current thinking is that a single application is generally appropriate for a combination product, the guidance notes, with the primary mode of action (PMOA) determining which type of marketing application should be submitted (e.g., a PMA, De Novo, or 510 (k) for a device-led combination product, an NDA or ANDA for a drug-led combination product or a BLA for a … [7], FDA has been responsive in accommodating tandem reviews. The device facilitates more effective treatment or diagnosis of life-threatening or debilitating diseases or conditions. PDG® is a federally registered service mark of Pharmaceutical Development Group, Inc.Pharmaceutical Development Group (PDG) is a subsidiary of Biotech Research Group Corporation. Big pharma companies are hiring “their own device groups to develop devices specific to their therapies to set them apart in the marketplace”.[16]. What types of HF studies might need to be conducted for the combination product? There has been an explosion of new and innovative medical device products launched in the US and global markets over the last 5 years. However, in 2002, FDA established the Office of Combination Products (OCP) to address, among other issues, ambiguity on how to classify products that cross Center jurisdictions. However, in 2002, FDA established the Office of Combination Products (OCP) to address, among other issues, ambiguity on how to classify products that cross Center jurisdictions. Pharmaceutical Development Group (PDG) is a subsidiary of Biotech Research Group Corporation. This injection history can be emailed directly to the patient or physician, so it is an added feature that benefits the patient and allows oversight by the healthcare provider. Office of the Commissioner,Office of Clinical Policy and Programs,Office of Combination Products, Center for Devices and Radiological Health, Center for Biologics Evaluation and Research, An official website of the United States government, : It is also broken down by specific products. General themes of these amendments include enhancing clarity, predictability, efficiency, and consistency of premarket regulatory expectations for combination products, including by ensuring that Agency components and staff coordinate appropriately on premarket review of these products, and that Agency thinking is aligned in conducting these reviews. Therefore, there are many critical factors[14] to consider for patient safety that are not normally considered for patients in a clinical setting, i.e can they safely dispose of the product, can they safely self-administer, can they follow the included directions for administering? Let CP Pathways guide you in building a combination product regulatory culture that unites the best of biopharma and device strategies and people. This market is expected to grow to $31 billion in 2019, with a compound annual growth rate (CAGR) of 7.1% from 2014 to 2019.”. The 505 (b) (2) development pathway provides far more efficient drug development for follow-on products by allowing reliance on certain external data and information for the NDA. In September 2015, Bayer Healthcare announced (FDA) approval of its at home use drug delivery device, BETACONNECT®, a first-of-its-kind electronic autoinjector indicated as a treatment for relapsing-remitting multiple sclerosis (RRMS) to deliver their drug Betaseron®. FDA is publishing this guidance as part of its efforts to implement Cures Act section 3038 and in keeping with the Agency’s long-standing commitment to transparency, efficiency, and regulatory consistency, to facilitate development of safe and effective combination products. Representative users test the product to “help eliminate or mitigate any potential use-related hazards”, that may not be evident during the design planning. HF testing is usually done alongside or prior to clinical testing, however not all sponsors are aware of this requirement. Above all, if you need help with a pre-submission request, RFD (request for designation), or combination products generally, contact PDG! or. While not approved as of this writing, innovations such as these are increasing in prevalence with growing consumer expectations related to ease of use, less restrictive living and integration with smart technologies.[15]. cross labeled . As recently as September 21, 2016, FDA released a draft guidance for the Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices. via the 505(b)(2) regulatory pathway. Because of the substantial amount of research and data that is required, 505(b)(1) NDA … FDA is assessing industry reaction to a proposed rule on determining a combination product’s primary mode of action – a key concern related to where and how the products are reviewed. The 505(b)(1) regulatory pathway is the traditional New Drug Application (NDA). The pipeline of combination products promises unprecedented drug delivery innovations. Should the wrong PMOA be identified, the application may be delayed by the Office of Combination Products (OCP). “According to BCC Research, sales of the drug-device (segment of combination products alone) reached $21.4 billion in 2013 and $22 billion in 2014. Section 3038 of the 21st Century Cures Act, enacted in December 2016 (P.L. The regulatory pathway for combination medical products in the United States is not always clear, and there are no specific FDA regulations that govern approval of combination products. Food and Drug Administration As more products utilize sophisticated technology, FDA continues to respond in kind. Prior experience in working with the 505(b)(2) regulatory pathway facilitates the use of appropriate data from the literature, product labels, and OTC monographs to reduce the clinical requirements for approval of the final combination product. Definition of combination products - US. In order to qualify for participation in the Breakthrough Devices Program, a device must meet two key criteria: 1. [3], As you might imagine, combination products face unique regulatory hurdles regarding review, pathway, post-market regulation, etc. See PDG’s previous articles on FDA’s pre-sub program for how and why this program might benefit the developer of a combination product. It is important to have experts on both the drug and device side, not only for the purpose of initial regulatory strategy, but to ensure that through the entire product life cycle, (from design to manufacturing to market), the combination product meets or exceeds quality and regulatory requirements. IMDRF is a voluntary group of medical device regulators from around the globe, including FDA, who have come together to build on the strong foundational work of the GHTF. The US Food and Drug Administration’s (FDA) Office of Combination Products (OCP), established by the Medical Device User Fee and Modernization Act of 2002 (MDUFMA), is the regulatory body responsible for covering the regulatory life cycle of combination products, including serving as a focal point for combination product issues, developing guidances, … Understanding how to bridge your drug to an approved drug and what types of information are appropriate to use is critical to getting your drug approved. This pathway is used to obtain the approval of a new drug whose active ingredients have not previously been approved. FDA: “Combination products are therapeutic and diagnostic products that combine drugs, devices, and/or biological products.” • Can be . Regulatory approval or clearance of a combination product revolves around determination of the primary mode of action (MOA). What is the role of HF studies as compared to other types of clinical studies? For the purpose of this article, we will focus on the drug/device segment. Present Regulatory Pathway for Biologics in US: To avoid unnecessary delays and gain speed to market through ‘right the first time’ regulatory submissions for a combination product, sponsor companies must understand the various pathways for which a combination product can travel. [11], Because HF testing is still relatively new, inquiries to the FDA include:[12]. Jodi Hutchins is an Independent Regulatory and Quality Consultant with over 15 years of global medical device registration experience, to include FDA 510(k) submissions. See below for a graph of current and expected North American sales for drug device combination products. Pharmaceutical Development Programs: Implementation and Oversight, Investigational New Drug Application (IND)/Special Protocol Assessment (SPA), Pre-NDA Meetings and NDA Submissions: 505(b)(1)/505(b)(2), Generic Drugs: 505(j) ANDAs and Potential Diversification, Device Pre-submission Meetings and Reviews, Combination Device and Drug/Biologic Submissions, Supplier/Vendor Selection and Qualification, International Health Authority’s Websites, An Effective Strategy for IND Pharmaceutical Product Development, Regulatory Consulting- the Missing Piece to Your Puzzle, An Introduction to Clinical Trials and Resources for Continued and Intermediate Learning, EMA Drug Post-Marketing Safety Surveillance Changes, US Impact and Compliance Assistance. [10] HF studies are generally conducted to evaluate user interfaces. As you might imagine, combination products face unique regulatory hurdles regarding review, pathway, post-market regulation, etc. [4] [4] While OCP is not a review/approval Center for your combination product, they do provide general guidance on which pathway is best for your product and to ensure combination products have general oversight. If unable to submit comments online, please mail written comments to: Dockets Management In a world in which we are continuously challenged to operate more efficiently and immersed in rapid technological advances, it should come as no surprise that one of today’s fastest growing medical product segments are combination products. Regulatory Pathways of Drug-Device and Device-Drug Combination Products in the EU – Journal 31 NSF: Ann Arbor, MI. As you can imagine, this type of submission requires extensive research including both clinical and nonclinical studies to prove the product’s safety and efficacy for the indication being sought. Charles Jaap is Vice-President of Operations and Business Development for PDG®, a global pharmaceutical and medical device consultant with extensive experience in the strategic development of drug products and medical devices. Not surprisingly, “High incidence rates of chronic pain causing diseases, prostate cancer, diabetic retinopathy, cardiovascular diseases, colorectal cancer, asthma, obesity along with rapidly aging global population also form the key drivers for the global drug device combination products market.”[2] However, much of the information herein may be extrapolated to other facets of combination products. [13] Development of drug/device combination products are usually for convenience of the patient to self-administer, i.e. To reach its ultimate goal of multinational approval, the company needed to develop a regulatory strategy by which the classification of its product as a combination device could be preserved, country-specific clinical trials could be avoided, and the approval process could be expedited. There is not always a clear-cut pathway. single entity, Co-packaged . We do so because we are so often called upon to address drug delivery devices. Combination products are therapeutic and diagnostic products that combine drugs, devices, and/or bi The .gov means it’s official.Federal government websites often end in .gov or .mil. 2. To be considered a combination product by FDA, there must be two or more regulated components, (i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic) that are physically, chemically, or otherwise combined or mixed and produced as a single entity, or two separate products that are packaged together and per proposed labeling are intended for use together to achieve a desired effect. The draft guidance was prepared via the support of the International Medical Device Regulators Forum (IMDRF), formerly the Global Harmonization Task Force (GHTF). In fact, the agency recently released a draft guidance entitled, “Software as a Medical Device (SaMD): Clinical Evaluation.” The draft guidance focuses on establishing the scientific validity, clinical performance, and analytical validity for these types of applications. Globally, separate regulatory pathways for innovator products and generic Agency policy regarding postmarket regulation of combination products is outside the scope of this guidance. For the drug development side, expect consumer study requirements such as label comprehension (understanding the key label message), self-selection (choosing the right product), actual use (using according to labeled directions), or HF (interacting with the product). General themes of these amendments include enhancing clarity, predictability, efficiency, and consistency of premarket regulatory expectations for combination products, including by ensuring that Agency components and staff coordinate appropriately on premarket review of these products, and that Agency thinking is aligned in conducting these reviews. IMDRF has essentially consolidated forces with a focus on accelerating international medical device regulatory harmonization. The opinions and statements in this paper are solely those of Charles Jaap and Jodi Hutchins and do not necessarily reflect those of PDG©. They caution against restricting combination products to either the premarket approval application or de novo pathways and favor greater discussions on the 510 (k) pathway, including the roles of general and special controls. [9], Whether your combination product is deemed a drug or medical device for regulatory purposes, testing for both may still be required. The app is used to set reminder alerts for the next injection, with a calendar of all injections that have been scheduled, recorded, or missed. According to Bayer “all a patient will have to do is prepare the Betaseron® syringes provided in the medication pack and use BETACONNECT® for a more convenient and effective delivery”, that allows patient to select the speed and depth of injections as well. If it’s deemed the drug is the primary mode of action, it will be reviewed by CDER (Center for Drug Evaluation and Research) and likewise, if its deemed the device is the primary mode of action, CDRH (Center for Devices and Radiological Health) will orchestrate the review. Not for implementation. FDA on Prefilled Syringes and Combination Products — What This Means for You ... and melted into the skin and of course I was learning with the innovator as to what kind of things are applicable in a regulatory world, trying to get this thing through the pathway here. Note that transdermal patches lead the way. Contains non-binding recommendations. She held her most recent position for 9 years, as QA/RA Director for a worldwide distributor of medical devices. [5] It should be noted that the RFD process is currently undergoing changes to include the possibility of a pilot Pre-RFD. A quick search for innovative combination products found a tattoo-like skin patch for diabetes sufferers that can detect glucose levels in its wearer’s sweat and accordingly will deliver a drug as needed. Key Point Summary: 1. The medical device industry is now capable of using 3D printers to produce everything from prosthetic parts to artificial knees to surgical tools. The earlier described BETACONNECT® will also feature an app to upload data to a smartphone or computer. The drug and device industries recognize the demand for more convenience in our fast-paced lives and more advances in our tech savvy world, so they see value in investing money in new product design and development. We have experts on staff with experience in drug, device and combination product registrations to assist you with all of your consultancy needs. Implement a plan that gets everyone on board. Once you know what regulation applies to your product … 3 FDA Performance Report To Congress: FY 2014: Office of Combination Products. Pharmaceutical Development Group, Inc. All Rights Reserved. pre-filled syringes, insulin-injector pens. The determination is based on “primary mode of action” (PMOA) of the combination product. Rockville, MD 20852. Drugs Can be Approved via One of Three Regulatory Pathways New drug products can belong to one of two broad categories: brand new drugs and identical or close copies of previously approved drugs, also called generics. Take the first step We’ll work with you to assess your product, strategies, team and timelines and develop a package that suits your needs. A combination product invokes an FDA regulatory requirement (21 CFR 300.50) that generally requires the developer to demonstrate that a population exists who would be served by the combination, and that each component of the combination contributes to the clinical effect of the combination product. [1] Combination products should not be confused with Fixed-Combination Drugs (FCDs), which are drug-drug combinations. Labeling products as sterile. You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5)). It’s critical to understand the main mode of action of your product as that will determine whether it will be regulated as a medical device or as a medicinal product (drug) in the EU. The device represents breakthrough technologies that have no cleared or approved alternatives already available on the US market; offer significant advantages over existing alternative devices; and for which availability is in patients’ best interes… combination products may be regulated as both a drug and a device • ANVISA determines the designation and regulatory pathway / requirements for combination products on an ad-hoc, case-by-case basis Emerging Regulations in Emerging Markets Examples • Chinese Government Circular # 16 (2009) refers to General themes of these amendments include enhancing clarity, predictability, efficiency, and consistency of premarket regulatory expectations for combination products, including by … Overcoming Combination Products Regulatory Challenges Until now, combination products are more often handled inconsistently in different jurisdictions as drugs and/or devices. CP Pathways’ principle consultant is Doug Mead – a highly experienced combination products regulatory expert with a diverse background in drugs and devices, including their design and testing, risk analysis, human factors testing, stability testing, and clinical trial real use patient handling assessments.Doug has a network of experienced combination product regulatory … US Regulatory Pathways for Bone Graft Products The required regulatory pathways by which bone graft products get to market, and the required data to support those pathways are varied. When is the appropriate time to perform HF validation studies? A combination product’s regulatory pathway generally depends on its primary mode of action (PMOA), recently defined in the 21st Century Cures Act as “the single mode of action of a combination product expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.“3,4 FDA’s Office of Combination Products (OCP) examines the product’s modes of action, determines which is the PMOA, and then uses that to a… (e.g., new drug product exclusivity, orphan status, or proprietary data protection when two firms are involved). 5630 Fishers Lane, Rm 1061 The guidance is intended to “assist drug sponsors and device manufacturers who are planning to develop new antimicrobial drugs and AST devices and who seek to coordinate development of these products such that the AST device could be cleared either at the time of new drug approval or shortly thereafter.”[8], Examples of combination products include pre-filled syringes, insulin injector pens, metered dose inhalers, transdermal patches, drug eluting stents, catheters with antimicrobial coatings, infusion pumps, medicated wound treatments and therapeutic orthopedic implants. Human Cell or Tissue Products The US Code of Federal Regulations Title 21, part Suttons Creek creates a successful pathway to global regulatory approval and commercialization of your combination products with the following core approaches to our partnerships. 2. Search for FDA Guidance Documents, Draft Guidance for Industry and FDA Staff, Recalls, Market Withdrawals and Safety Alerts, Search General and Cross-Cutting Topics Guidance Documents, Principles of Premarket Pathways for Combination Products. Before sharing sensitive information, make sure you're on a federal government site. The FDA outlined a new pathway for the expedited approval of medical devices, diagnostics and certain combination products that aim to improve upon the safety of those currently on the market. Integration of smart phone apps, global positioning technology and smart features built into devices and packaging are on the way. Thus ultimately, if the sponsor cannot or does not want to decide, the Office of Combinations Products will decide the most important aspect of the combination, either the drug or the device, through the Request for Designation (RFD) process. Dykeman said that there is a general belief in the field that device pathway is quicker and cheaper, but that isn’t always the case. The site is secure. This key piece of information determines the product’s regulatory pathway, and allows the sponsor to begin the process of submitting its drug device combination product for approval. Bill Welch says when developing a combination product, there are many things to be considered – relationships between device development and the pharmaceutical or biologic, early establishment of regulatory and clinical strategies, understanding user needs, determining product requirements, as well as device manufacturing variation. 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