2-Day In-Person Seminar (Code – GRCSEM-6229)
Preparation of FDA Submissions and Communicating with the FDA (INDs, NDAs, BLAs, ANDAs, PMAs, 510(k)s, IDEs, Post-Approval Supplements)
David R. DillsGlobal Regulatory Affairs & Compliance Consultant
October, 17 and 18, 2018
San Francisco, CA, USA
Getting a drug, biologic or medical device approved by the FDA is one of the highest hurdles in the development process. This seminar covers current FDA regulatory compliance and the approval process with respect to developing and marketing drugs, biologics and medical devices. A focus will be placed on relevant aspects of FDA regulations and the practical aspects of bringing a medical product to market. The course will initially cover the general context for medical device regulations. Later, a more in-depth discussion will begin to look at each of the submission categories in detail. FDA’s regulations, guidance documents, and how to prepare drug/pharma and medical device submissions will be covered in detail. This course will describe the submission process and the contents required by the FDA for a successful submission. It will also provide an understanding of the common pitfalls, delays, and possible preventive measures. Also described will be the type of activities a company can pursue while waiting for submission clearance.
Companies who want to market in the U.S., a Class I, II, and III device intended for human use, for which a Premarket Approval (PMA) is not required, must submit a 510(k) submission to FDA unless the device is exempt from 510(k) requirements of the Federal Food, Drug, and Cosmetic Act (the Act) and does not exceed the limitations of exemptions in part .9 of the device classification regulation chapters. A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective (substantially equivalent) to a legally marketed device that is not subject to PMA. Submitters must compare their device to one or more similar legally marketed devices (predicates) and make and support their substantial equivalency claims. Until the submitter receives an order declaring a device SE, the submitter may not proceed to market the device. Once the device is determined to be SE, it can then be marketed in the U.S.
Several types of premarket submissions can be made to FDA. In order to legally market a device in the US, the most common forms of premarket submissions to FDA are the 510(k) premarket notification submission and the PMA premarket approval. Another lesser known premarket submission is the de novo submission. Each of these submission types result in a determination by FDA that clears [510(k)], approves [PMA], or grants [de novo] marketing rights to the successful submitter. Other submissions to FDA include Pre-submissions (Pre-subs), Investigational Device Exemptions (IDE), Humanitarian Device Exemptions (HUD), and Master Files, to name a few.
The premarket approval (PMA) is the second most commonly used pathway to market for medical devices in the United States. In fact, nearly 10% of medical devices are brought to market using this important pathway. However, since the PMA is reserved for the highest “risk” (i.e., class III) devices, the requirements are much more complex compared to more common premarket notification (PMN) a.k.a. the 510(k). This makes for a confusing process, and not having a concise, data-driven submission can seriously jeopardize your product approval efforts. Fortunately, there are ways to ensure that your PMA meets regulatory requirements while clearly outlining the therapeutic benefits of your product.
Using real examples, this course will outline some of the common pitfalls experienced during the PMA process, while providing the tools needed to ensure success for your submission. Additionally, you will receive a brief primer in the difference between device, drug and biologic clinical trials to establish a foundation for crafting your PMA.
An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support requests to legally market the device.
Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated. Unless exempt from Investigational Device Exemption (IDE) regulations, an investigational device must be categorized as either a Significant Risk (SR) device or a Non-Significant Risk (NSR) device. This course will cover all aspects of the approval/submission process, the application and IDE and GCP regulations.
Nonetheless, this course will give participants the necessary overview of the US Food and Drug Administration’s (FDA) current responsibilities, procedures, guidance documents and regulatory pathways that affect the review and approval of chemical drugs, biologicals, biopharmaceuticals, biosimilars and chemical generics. Using the ICH Common Technical Document (CTD) module format outline, significant Chemistry Manufacturing and Controls (CMC), Nonclinical and Clinical areas will be analyzed and discussed, as a basis for strategic planning for both submitting INDs, NDAs, BLAs, ANDAs, and post-approval supplements, as well as for holding key meetings with the FDA. Similarities and differences between clinical INDs and market approval dossiers, and between the various market approval dossiers (NDAs, BLAs, and ANDAs) will be discussed. Other topics to be discussed include Fast Track pathway, comparison of chemical generics with biosimilars, FDA’s commitments under the User Fee Acts (PDUFA, BsUFA, GDUFA) and FDA’s evaluation of industry’s performance in meeting its requirements and expectations for review of drug products.
This course provides a comprehensive approach to the preparation and submission of documents to the FDA for approval of drug products. Participants receive a foundation of knowledge about the drug approval process, submission preparation, and the underlying scientific and regulatory principles involved. Guidelines for each aspect of research are provided, as well as information on the structuring and assembly of INDs, NDAs, and post-approval documents. Information on maintaining on-going relationships with the FDA is also discussed.
The course enables regulatory affairs professionals to prepare concise documents, provide the FDA with necessary information, and obtain rapid product approval. or decades, the regulation and control of new drugs in the United States has been based on the New Drug Application (NDA). Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization. The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA. Learn how to address and comply with post-approval supplements and changes to your drug and device submissions. This and much more will be addressed during our seminar on preparing and submitting “high quality” PMA, 510(k), IDE, IND, BLA NDA and ANDA submissions and regulatory filings.
Why should you attend (Course Objective)?
- What do the regulations say?
- Navigate the FDA drug and device approval system
- Prepare, construct and submit well-written IND, NDA, BLA, PMA, 510(k) and IDE submissions and regulatory filings
- Navigate the FDA review process
- Identify the required regulations and guidance documents for drug and biologic submissions
- Use regulations and guidance documents to outline and construct a variety of drug and biologic submissions
- Formulate a working knowledge of regulatory submissions, publishing, and style guides
- Create checklists that encompass timelines and sections needed from contributors
- Strategic and technical guidance for drug and medical product development and regulatory review
- Regulatory policy guidance
- Regulatory Strategy planning and communications
- FDA 510(k) submissions for obtaining FDA clearance
- FDA Investigational Device Exemption (IDE) submissions for US clinical studies
- FDA Requests for Classification and Requests for Determination
- FDA Pre-Submission (Pre-sub) meetings
- Attendees are encouraged to bring examples of their work from the functional area on the various topics as applicable for group discussion
- Challenges and possible solutions will be discussed, and examples will demonstrate how the requirements can be put into practice
- Where does the PMA fit into the medical device universe (e.g. how to decide whether to use the PMA or another pathway to market)?
- How can the PMA be your friend (e.g. when a PMA is actually preferred over a 510k)?
- What are the ‘required contents’ of a PMA submission?
- How to decide amongst the types of PMA submissions (e.g. traditional, modular, streamlined, etc. and what are the advantages and disadvantages of each)?
- What is the Summary of Safety and Effectiveness Data (SSED) and how is it used?
- What are the differences in clinical trials for devices compared to drugs and biologics?
- How can we design device clinical trials to maximize our success to market?
- When can we combine pathways via label expansion?
- Want to avoid the PMA? Consider the De Novo – using classification to your advantage!
- How to use the PMA beyond the device world? i.e., using combination products: PMA+NDA/PMA+BLA, etc.
- Define basic terms related to device research
- Locate applicable regulations
- Determine when an IDE is required
- Describe Sponsor & Investigator responsibilities
- Know contents and submission process for an IDE Application
- Conduct IDE, PMA and 510(k) submission management activities
- Regulatory strategy and regulatory planning for effective IND, NDA, ANDA and BLA submissions
- Preparing for and conducting effective and efficient FDA meetings and communications
- When to address and submit Post-Approval Supplements
- Review and discuss pain points, challenges and solutions
Learning Bonus: Upon completion of this course, attendees will have an understanding of the framework for FDA submission regulations and an approach on how to construct a submission. An appropriate submission strategy is necessary to legally manufacture a product in the US market. The course focuses on how a company’s product situation needs to be evaluated in order to determine the correct interpretation of the submission requirements. Emphasis will be placed not only on regulatory aspects, but on the overall medical device and drug product development strategy and environment. Creating an effective submission strategy will help your company avoid spending unnecessary time and money by avoiding an inappropriate path.
Additional Bonus: Exercises and presentations from the FDA will be used to reinforce the key concepts from the course presentation. Attendees will receive extensive course notes that can be used as reference material once the course is completed.
Who will benefit:
Personnel in the pharmaceutical, biopharmaceutical, biologics and generic drug industry who are involved in preparing FDA submissions (INDs, NDAs, BLAs, ANDAs, post approval supplements) will find this course to be of particular benefit. Those who need to interact with FDA staff, including Project Managers, Regulatory Affairs, Clinical, Nonclinical, Manufacturing, and Quality personnel, will also find this course extremely useful.
This 510(k), PMA and IDE medical device submissions will be most valuable to medical device/product professionals who need an understanding of how to get medical devices into the US market while respecting FDA regulations. The course is geared toward professionals that are newer to the industry or who need to gain an understanding of submissions for the first time. Engineers, managers, supervisors, scientists, technicians, and other personnel involved in product development, manufacturing, quality assurance, or regulatory affairs that do not have an in-depth knowledge of medical device submissions will benefit from this course.
- Research & Development Departments
- Engineering Departments
- Quality Assurance Departments
- Regulatory Affairs Departments
- New Product Development
- Marketing Departments
- Mid-level and Senior Management
- Project Leaders
- Professionals involved with premarket notification to the FDA
- Clinical Operations & Trial Management
- Clinical Quality Assurance
- Clinical Research Associate
- Clinical Research Coordinator
- Clinical Research Investigator
- Data Management
- Drug Safety
- Medical Affairs
- Medical Writing
- Project Manager
- Quality Control
- Regulatory Affairs
- Study Site Compliance
- The recent changes in the 510(k) program and guidance documents relating to both 510(k)s and PMAs
- How to identify and assess the regulatory requirements
- How to meet the regulatory requirements in a systematic, integrative manner
- How to increase a 510(k) and PMA submission quality
- How to format succinct and comprehensive 510(k) and PMA submissions
- When to submit a 510(k) for a new or modified product
- Types of 510(k) submissions and when to use each
- What is the submission process?
- What is contained in a 510(k) submission package?
- How to know whether clinical data is required.
- How is the submission package assembled?
- User fees and 510(k) submissions
- How to interact with the FDA and the reviewer
- What to do if you make a change to your device
- What is “regulatory logic” and how can we use it to our advantage?
- What is and is not a regulated medical device?
- How do we “design” or labeling (i.e., stated claims vs. inferred/implied claims)?
- How can we “advertise” off-label use?
- What is competitive regulatory strategy (i.e., how can I use regulation as a barrier to entry to my competition)?
- What is the medical device classification system?
- Why do we have a classification system? Why is it important?
- How do I determine classification?
- Can I change classification?
- How can I use classification to my advantage?
- How does classification vary in other parts of the world?
- What are the major pathways to market?
- Premarket Notification a.k.a. 510k
- Premarket Approval (PMA) de Novo regulatory pathway and when to use it
- Which do I choose and when?
- Must I use only one? Can I mix and match?
- What is the Pre-Market Notification (PMN) a.k.a., 510k?
- How can I use the 510k to my advantage?
- What does substantial equivalence really mean?
- Why are many 510(k)’s rejected and how do I avoid being in the majority?
- What types of 510k’s exist and how do I choose?
- What are the two most important components of a successful 510k?
- When and how can I use the split- and multiple predicate strategies safely and effectively?
- What is predicate creep?
- If I change my device, must I tell FDA (special 510k vs. letter-to-file)?
- What is the future of the 510k?
- Steps to develop a PMA submission strategy
- Best practices of quality system information for PMA applications
- What to expect during a submission review
- Preparation needed for an advisory panel meeting
- Tips to prepare for an inspection
- Ins and outs of BIMO inspections
- How to deal with unexpected clinical outcomes, animal test results, and adverse panel recommendations
- Needed supplemental submissions for approved PMAs
- Where does the PMA fit in the medical device universe?
- Why PMA’s are rejected and how do I avoid being one of them?
- How does the 510(k) compare to the PMA? Can I do both?
- When is an IDE ‘required’ and when is it not (i.e., SR vs. NSR)?
- What types of PMA’s exist and how do I choose?
- What goes into a successful PMA?
- When do I need a clinical trial and how do I design one?
- Key steps for the De Novo Pathway
- What is the de novo and how does it compare to the 510k?
- Why is the de novo the fastest growing pathway to market in the US?
- How can I use the de novo to my competitive advantage?
- Communication with FDA: The Pre-Submission Process
- When and how should I communicate with FDA?
- What is a pre-sub and should we use it?
- What is a successful pre-sub and why are most not successful?
- How early should we talk to FDA?
- What do we need to include/should we include in the pre-sub?
- Should we meet in person? How do we prepare?
- What happens after the pre-sub? Are the results binding?
- What are the regulatory challenges of combination products, tissue engineering and biomedical nanotechnology?
- Where can I find additional information?
- Definitions and Marketing Overview
- Pre-Submission Meetings
- Clinical Investigations of a Medical Device
- IDE Exemption
- Understand the application process and administrative action with your IDE
- Know the responsibilities of the sponsor
- IRB review and approval and expectations
- What records and reports are expected and required
- IDE refers to the regulations under 21 CFR 812
- Know the procedures involved with the clinical studies and expectations
- Understand that if the study involves a significant risk device, the IDE must also be approved by FDA
- SR/NSR Determination and the IDE
- The following topics are discussed throughout the course:
- How do I integrate regulatory strategy and reimbursement strategy?
- What goes into an international regulatory strategy?
- What is regulatory risk and how do I factor it into my regulatory
- How can I use guidance documents to my competitive advantage?
- What is usability and where does it fit into regulatory submissions?
- What’s the difference between writing a regulatory submission
vs. designing a regulatory submission?
- Learn the appropriate and expected regulatory strategies and
guidelines for your drug and device submissions
- Pre-submissions are made to the FDA in order to request FDA
- Pre-subs are used for various reasons including meeting
requests, to study risk determination, for submission issues, and for FDA
feedback to specific questions related to a pending submission or protocol
- The de novo pathway for device marketing rights was added to
address novel devices of low to moderate risk that do not have a valid
- Upon successful review of a de novo submission, FDA creates a classification for the device, a regulation if necessary, and identifies any special controls required for future premarket submissions of substantially equivalent devices
- Review and approval procedures for drug and biologics submissions/regulatory filings
- Current Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. Because a sponsor will probably want to ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement. The IND is the means through which the sponsor technically obtains this exemption from the FDA. There are three IND types.
- FDA Division Information: Submission Basics; Outlining the submission, creating the Table of Contents, timing of submission/timelines, contributions from other departments, editing, style guides, templates, supportive documents, QA’ing the submission
- Publishing the Submission: Submission publishing basics; Copies (how many to make and keep); Introduction to electronic publishing requirements
- Tracking the Submissions: Creating the index history; Creating an issues log
- Common Technical Document Format Regular Copy
- Pre-Market: FDA Meetings (Type A, B and C): Pre-IND, Phase I, Phase II, End of Phase II, requesting the meeting, preparing the meeting package, meeting minutes; The IND Submission; Routine IND Submissions: Clinical, Non-Clinical, CMC, Annual Reports, Investigator Brochure updates, protocol /protocol amendments, Investigators; Additional IND submissions: Fast track, orphan drug, special protocol assessment
- Marketing Application: NDA in a CTD Format
- NDA Forms and Electronic Submissions
- Guidance Documents for NDA’s and ANDA’s
- NDAs and BLAs: Filing Refusal to Accept Application for Filing From Applicants
- The Generic Drug Approval Process
- What Is the Approval Process for Generic Drugs?
- Applicant information
- Product/Manufacturing information
- Preclinical studies
- Clinical studies
- The resources for application reporting and applications procedures apply to IND applications for both clinical research and clinical treatment
- Pre-Investigational New Drug Application (Pre-IND) Consultation Program
- Legal Basis for FDA’s Authority to Regulate Chemical Drugs, Biologics and Biopharmaceuticals
- Overview of human medicine regulation by the FDA
- Drug regulatory pathways granted to the FDA by U.S. Congressional laws
- Human medicine distinctions: chemical drugs vs. biologics, CDER vs. CBER, generics vs. biosimilars
- FDA Regulatory Drug Development Review and Approval Process
- FDA’s requirements/expectations for CMC, Nonclinical, Clinical content from Phase 1 through market approval
- Differences in the FDA regulatory review and approval pathways for NDAs, BLAs, ANDAs and biosimilars
- Accelerated and fast track FDA review opportunities
- Meeting with the FDA
- PDUFA, GDUFA and other meetings with the FDA - justified not entitled
- Risk assessment – when should you have a meeting with the FDA
- Lessons learned of what to do/not to do
- Critical Importance of FDA Submissions and Communication during the IND Stage
- What the FDA is looking for in IND submissions/amendments - avoiding the ‘clinical hold’
- Forms, format and content required during the clinical stages
- Strategic value of the critical meeting with the FDA
- Critical Importance of the FDA NDA/BLA/ANDA
- Dossier Preparation
- Need to avoid the Refusal to File
- What the FDA is looking for in the market application dossier – forms, format, content
- Strategic value of the Pre-NDA/BLA submission meeting with the FDA
- FDA Review and Approval of the NDA/BLA/ANDA Submission
- First milestone – avoiding the ‘Refusal to File’
- Intense interactions with the FDA covering CMC, Nonclinical and Clinical
- Race to meet the time clock – avoiding the Complete Response Letter
- Post-market Approval Submissions and Interactions with the FDA
- Supplements for changes in CMC and Clinical, and required FDA reporting/updating
- Honoring post-market approval commitments and ongoing adverse event reporting
- Navigating the Rich FDA Website Resources
- On-line resources for Drugs
- On-line resources for Biologics
- Insights into the FDA NDA/BLA review process
- Practice on a project relevant to participants’ organization
- Interactive Exercises and Discussions
- Drug and Medical Device Submissions and FDA Communications and Meetings
- Questions and Summary
David R. Dills, Global Regulatory Affairs & Compliance Consultant currently provides regulatory affairs, compliance and quality consultative services for early-stage and established Class I/II/III device, In Vitro Diagnostics, cosmetics and bio/pharmaceutical manufacturers on the global landscape, and also has an accomplished record with more than 25 years of experience in the areas of Regulatory Affairs, Compliance and Quality Systems. He has been previously employed, with increasing responsibilities by medical device manufacturers and consultancies, including a globally recognized CRO and has worked directly with manufacturers engaged in compliance remediation activities and services involving consent decrees, CIA’s, warning letters, 483 observations, and customer generated compliance events, and prepares for and conducts QS and regulatory audits.
He has been directly involved with constructing, reviewing, and/ or remediating regulatory submissions, including 510(k), PMA, IDE applications, IND, BLA and NDA submissions, preparing Supplements, Amendments, U.S. Agent, works closely with the key stakeholders and Agency/Center Reviewers regarding submission meetings and negotiations; clinical affairs and study submissions; and provides regulatory submissions and post-market project leadership and guidance covering different therapeutic and medical specialties based on classification.
Mr. Dills has a strong background in the interpretation and applicability of FDA regulations, including 21 CFR 210/211, 820 QSR/cGMP, Quality System implementation and compliance requirements, GxP training, leads and directs activities for the registration and approval process and working with Agencies in Asia Pacific, EU and The Americas, including but not limited to FDA, European Medicines Agency–EMA, MHRH, ANVISA, PMDA, MOH, SFDA, TGA, and Health Canada; and defining and executing regulatory compliance, risk mitigation and remediation strategies in response to inspection findings. Additional activities include Pre-FDA Facility Inspections, Mock Audits/Due diligence and assessing state of readiness for Pre-approval inspection (PAI/PMA), proof of management oversight, facilitate and direct efforts for remediation planning and monitoring, and assessment of the critical sub-systems, records and document controls; and strives for reduction of regulatory compliance risk for companies.
Mr. Dills has authored and published validation, regulatory and compliance-related articles, commentaries and technical guides, and is an accomplished global industry presenter. Mr. Dills’ academic degrees include Environmental Science and Biology. He is a former Chair and Co- Chair of ASQ’s Section 1506 and associated with the Biomedical Division, RAPS, AdvaMed, PDA, ISPE, and other industry working groups.