Wednesday, January 26, 2011

510(k) Costs Can be Misleading

510(K)  COSTS  DISCUSSIONS  CAN  BE  MISLEADING

A discussion of a report on the multi-million dollar costs of 510(k)s is showing up on several websites/blogs. As it stands it can be highly misleading. While some companies may in fact have spent that total dollar amount cited, $24 Million USD, to get a product to the point where it has received a 510(k)clearance, to say 77% is tied to regulatory costs is very misleading. To arrive at those figures, those costs have to include features, documentation, engineering, testing, validation, personnel salaries, et al, most basic design, prototyping, testing, and production, et al,  activities that may be required under the cGMPs but are really related to normal design / R&D, pre-production and production activities, and product / use safety and quality.
Does any one seriously argue that many bench / functional testing, biocompatibility testing, sterilization, documentation systems, validations (including software), the other basics (including principles of Shewhart, Deming, Juran, et al) required under the cGMP quality management systems and its infrastructure, and yes, some clinical trials, should not be required? I've worked for years (28+) on medical device projects (the last 16 as a consultant), 510(k)s, validations, and unless the above are added to the equation, the figures quoted and attributable to FDA regulatory / clearance costs are completely unrealistic.
I for one would not want a device used on me or my loved ones that had not proved its safety and quality by such testing, and manufactured, labeled, tested / validated, packaged, and sterilized under documented / validated systems. True, some points raised about inefficiencies, uncertainties, delays, personnel qualifications, unnecessary or redundant activities, et al, are valid (but nowhere near the dollars implied), and not just on the FDA side, but also on the manufacturer's side, including their submissions. Some companies even report other companies' violations to the FDA to "level the playing field".
The majority of the Stanford Report itself raises legitimate questions, and certainly the conclusions of EU / other 'reputable', regulatory bodies should be strongly considered by the U.S. FDA, 'tho there are dangers (remember the drug thalidomide). However, a key point on costs, page 28, leaves the reader to guess what really contributes to the costs per month due to delays (idle personnel, borrowing costs / interest on loans, lost opportunity costs, or ...). In fact, the last sentence on that page opens up major questions ("likelihood", "self-selected" ... ) that beg answers to really justify the headlines given this study.
Many requirements work to a company's advantage, e.g., design control and fast cycle development, documentation and liability / IP / minimal "reinventing the wheel", reduced recalls (some recent events w/ treated wood pallets and odor- contaminated product for two major pharma companies come to mind). Of course such benefits are only realized IF (a big 'if') companies use them for business reasons, not just to satisfy regulatory / bureaucratic procedures.

-- John E. Lincoln, Medical device / cGMP consulting:  http://www.jelincoln.com/


Note:  The FDA-related cost were recently restated in a 2018 article:

Interventional Cardiologist Sees Negative Trend in Innovation: Despite Decreases in CVD Mortality 
"Also, the current cost to clear and approve a medical device in the U.S. is $31 million on average to bring a 510(k) product from concept through clearance, with $24 million spent on FDA-dependent/related aspects."  
-- https://www.policymed.com/2011/12/interventional-cardiologist-sees-negative-trend-in-innovation-despite-decreases-in-cvd-mortality.html

I believe my above comments still apply. - JEL

Note:  Most 510(k)s do not require clinical trials for FDA clearance. However, PMA's do for FDA approval.  Clinical trials can add thousands to millions, and years, to obtaining marketing authority.  But for many involving clinicals, it's still hard to justify a $24M price tag.  Pharmaceuticals are a totally different issue, but with 510(k)s we're talking devices.  - JEL 09/06/2023

Address Concerns in FDA's August 510(k) Task Force Findings

U.S. FDA'S 510(K)  WORKING  GROUP  FINDINGS, AUGUST 2010

As I am actively involved in compiling and submitting 510(k)s for clients, I find the August 2010 Working Group findings on 510(k)s to be a useful tool. Current indications are that these findings may not be immediately implemented.  However, they indicate some of the concerns re: the 510(k) process, and it may be wise to address those that affect product safety or indicate a company's efforts to increase device safety. My 510(k) submissions address many of the recommendations as if they were already implemented, especially in showing safety.  I do this primarily in two ways:  1) by including an ISO 14971-based hazard analysis / risk management file that includes an FTA and FMECA; and 2) by also performing an analysis of the FDA's MAUDE database for that family of product, and include that analysis in the submission. A complete product description seems like a "no brainer", but it's best not to assume anything and address even the most basic elements in a device description and in the SE / predicate(s) comparison matrix. It is also useful to incorporate principles from all regulated industries, not just devices, to address stated and anticipated FDA (and patient / clinician / user) concerns (e.g., the ICH Q-series principles and HACCP techniques). 

-- J. E. Lincoln and Associates LLC Medical Device Consulting:  http://www.jelincoln.com/

510(k) Projects

510(k)  PROJECTS

Many ask what's involved in obtaining 510(k) clearance for FDA-defined Class II medical devices for sale in the U.S.  The following is my typical response:

The product would essentially have to be almost the same, if not the same (substantially equivalent) as a previously cleared product (the predicate), with the same safety and efficacy issues. Any variation would have to be extensivelly tested by a testing company or lab. And to prove being identical, similar testing would also be required. Several international labs can provide a list of tests and their costs. These tests would be included in the 510(K) submission together w/ labeling, packaging, etc.

The FDA charges a fee to review a 510(k) with no guarantees, ~$4100.00+ USD (payable at time of submission; which can be reduced if the company can show it meets their definition of a small business a 60 day review). The parent company would have to be registered with the FDA (another fee of over $3000.00) and have a compliant cGMP system in place, and its suppliers would need the same. Consultants such as myself provide assistance in those areas as well (or the company, or another party could do) at additional costs.

Charges run the gamut, from lows in the $4-5000's to $10,000-20,000, or more, depending upon consultant and project complexity, with costs going higher if an IDE (Investigation Device Exemption) / clinicals are involved. IDE's can cost as much as a 510(k) since they address much of the same requirements. Some consultants, such as myself, make charges payable in 1/3s, with the first third up front, prior to start on the 510(k). Product risk analysis per ISO 14971 is usually several thousand dollars extra, unless a company already has their own. The company would be required to pay all the test fees and FDA fees, such as those mentioned above. And there would be no guarantees (the FDA is currently evaluating and tightening their 510(k) requirements).

Timeline:
  Lab testing ~2 mos
  IDE / Clinicals, if required, can take a year or more (check with CROs or appropriate consultants)
  Draft 510(K) ~2 mos (plus risk analysis, labels, etc) assuming availability of documentation
  FDA Review ~ 4 mos average

And there are no guarantees. If your product is basically identical to the predicate(s) then clearance is likely. Any differences raise the chance of the submission being found NSE (not substantially equivalent).  If such happens, there are several options:
1. Immediately refile a "de novo" application (if product is low risk);
2. Go back to the "drawing board" to address major issues, and refile another 510(k), with new fees;
3. File a PMA which is more expensive and can take several years.

J. E. Lincoln and Associates LLC Medical Device and cGMP Consulting:  http://www.jelincoln.com/

Note:  The FDA has moved toward encouraging more innovation to be allowed in 510(k) submissions and a move away from older technology (older 510(k)s based on older, less safe / effective technology) which has less patient benefit than most newer technology, but still allow such to be addressed under the faster 510(k) review process as opposed to the PMA process - modernizing the FDA 510(k) pathway:

https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-jeff-shuren-md-director-center-devices-and-4

Friday, January 21, 2011

Welcome to CGMP Issues

Welcome to my new blog -- CGMP Issues.  CGMP stands for current Good Manufacturing Practices, and specifically refers to the U.S. Code of Federal Regulations, Parts 111 (dietary supplements), 210/211 (pharma), and 820 (medical devices). We will discuss points of interest to the U.S. FDA-regulated industries, focusing on medical devices, but with some elements of pharmaceuticals, combination products, dietary supplements and related.  Please indicate your company's areas of concern and we will try to address them or direct you to the appropriate resource.  

The information provided in this blog is taken from sources and material which we believe to be reliable, and/or express the opinions of the writers and/or presenter.  In such condensed and generalized form, the material certainly should not be considered a complete study or report on the subject mater, especially as to how  it might relate to a specific company / user’s application.  Conclusions are based solely on available data, and the judgments and analysis of technical factors offered are not intended to replace the utilization of additional research and/or appropriate professional counsel in adapting material to a specific application.

© 2019  by J. E. Lincoln & Associates LLC.  All rights reserved.  Reproduction in whole or in part without written permission is prohibited. 



See my website:  http://www.jelincoln.com/