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FDA INSIGHTS NEWSLETTER
A newsletter of priceless wisdom from former FDA officials
510(k) Presents a Challenge to Medical Device Manufacturers
By Carmen Medina, M.P.H; Ph.D. ( c )
Former FDA Investigator
An expeditious review and approval of 510(k) submissions may be a thing of the past. FDA review and clearance of 510(k) applications has been revamped and under Commissioner Hamburg will receive greater scrutiny than ever before.
The 510(k) has always been a very simple mechanism for commercializing a device for which there is a predicate medical device already on the market. The Center for Devices and Radiological Health (CDRH) will be reviewing all 510(k) submissions with greater attention to safety and efficacy data—even when such data already exists for the predicate device or a “substantially equivalent" device already in commerce. This is all part of Commissioner Hamburg’s enforcement initiative which has been reinforced for medical devices as a result of several 510(k) incidents.
Without a doubt, FDA’s position related to the 510(k) submission, review and clearance process will cost the industry financially and from a new product perspective. The idea that additional scientific data would be needed for a device that is substantially equivalent to one that has been on the market for some time presents obstacles to innovation, particularly for the small medical device company.
The Center for Devices and Radiological Health Forum for International Medical Device Regulatory Authorities has and will continue to address the industry’s concerns regarding the 510(k) process and which applications are likely to receive additional review and/or require additional scientific documentation.
The Medical Device User Fee and Modernization Act (MDUFMA) addresses the costs associated with medical device submissions—FDA’s "FY 2010 Medical Device User Fee Small Business Qualification and Certification" guidance is presently available. The guidance document explains how your business may qualify as a "small business" allowing medical device user fees to be substantially discounted. Another great opportunity if you meet the criteria for a small business, is the one-time waiver program for first-time premarket application (premarket approval application, biologics license application, product development protocol, or premarket report). It is incumbent upon you to learn all you can before you submit a PMA or 510(k)—or the submission may be held up.
Strengthening the 510(k) process is just one aspect of the heightened scrutiny and analysis FDA officials will be exacting on all regulatory submissions. Consumers will likely benefit from this enhanced assessment process; although, there will be companies that simply can’t bring their new device product to market because of the additional costs this initiative imposes.
Take-home message:
- Learn what programs are available for first-time 510k and PMA submissions.
- Make certain the 510k contains all the scientific information necessary for the FDA to feel confident your device is safe and effective.
The Days of Aggressive FDA Enforcement Are Back!
By Carmen Medina, M.P.H; Ph.D. ( c )
Former FDA Investigator
Just when you thought the days of Dr. David Kessler’s aggressive compliance enforcement were a thing of the past—BEWARE because here comes FDA’s latest Commissioner, Margaret Hamburg. She’s tough, carries a big stick and it’s pointed right at all of you seeking new product approvals and sustainable commercialization. Ms. Hamburg recently stated that the FDA intends to reinstate its hard line field enforcement position which was characteristic of Dr. Kessler’s reign during his eight year tenure as FDA’s Commissioner under two separate presidents: Bush and Clinton.
In her own words: "When there are ongoing problems or when a problem emerges that has a serious impact on health, then we have to aggressively act."
Even Hamburg admits that the agency has been hampered by unreasonable delays when responding to violative conditions in the field. The impact that this has on public health can be considerable. Violations related to adulteration, quality assurance, false and misleading advertising and non-compliant labeling, particularly when left uncorrected for any significant period will invariably impact the health and safety of this country’s citizenry.
Multiple warning letters are also a thing of the past. From now on, companies that are repeatedly noncompliant can expect swift and aggressive enforcement actions—which can range from FDA issuing a corporate injunction, lodging hefty fines, and imposing a “seize and desist” order to suspending the firm’s operating license and securing a judicial consent decree. All of which translates to huge loss of credibility to the company and it’s executive management alongside significant loss of profits. Companies seeking new product approvals can expect long delays if violative conditions are uncovered during the clinical trial phase, the submission review process or during the pre-approval inspection (PAI). Each of these distinct regulatory milestones: clinical trial activity phase; submission (PLA, NDA. ANDA and BLA) review phase; and pre-approval inspection phase presents potential landmines. Non-compliant, violative findings during any of these key phases could pose a serious threat to the viability of the product and ultimately to the company’s survival.
Hamburg has vowed to ensure swift FDA action in order to expeditiously address violative situations and force companies to remediate quickly and address the FDA investigator’s findings. A commitment to US Public Health is clearly Hamburg’s mission and her skillful leadership will make FDA a force to be reckoned with in the years to come.
Top 10 Checklist for FDA Regulatory Submission
Jamie Sulley, Ph.D.
Former FDA Review Scientist
After having reviewed numerous regulatory submissions in my previous role as an FDA review scientist I developed my own list of expectations that I would refer to every time I began the review process. Here is an insider’s perspective which might provide additional insights as you prepare your regulatory submission.
THE TOP TEN:
- The sponsor should understand, present and explain how drug substance properties and formulation variables affect the performance of the drug product.
- The sponsor should identify the critical manufacturing steps, determine operating parameters, select in-process tests to control the process, and discuss how they plan to scale up the manufacturing process.
- The sponsor should be able to answer why the manufacturing process was selected?
- The sponsor should develop a scientific understanding of critical process and product attributes.
- Utilize knowledge gained over the product’s lifecycle to predict, justify, and present commercial plans.
- Evaluate and approve product quality specifications in light of established FDA standards (e.g., impurities, stability, etc.).
- Delineate how and why the excipients were selected?
- How was the final formulation optimized?
- What evidence supports compatibility between the excipients and the drug substance?
- Lastly, addressing the above questions in your NDA will:
- Result in a better understanding of sponsors' rationale for decisions and therefore, less misunderstandings
- Reduce reviewers' time spent in fact finding and summarizing NDA elements
- Help post-approval changes, by incorporating this information up front, sponsors will have the freedom to execute manufacturing process improvements for which they have demonstrated process understanding.
See next FDA newsletter article:
FDA Fights Battle on Two Critical Fronts
Carmen Medina, MPH, Ph.D. (c) |
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FDA INSIGHTS |
