MDUFA and its Impact on Medical Device Sector

The U.S. Congress passed Medical Device User Fee Act (MDUFA), where FDA is required to assign and collect fees from manufacturers of medical devices to evaluate the functioning and the usage of the device. for the purpose of fas-tening the analysis of the application of the drug. The Medical Device User Fee Modernization Act was (cid:977)irst adopted in 2002. The act focussed on innovative review process and reviewing capabilities of experts. Every (cid:977)ive years, MDUFA comes up with reauthorisation. The act was reauthorized in 2007 by reducing the application fee and introducing certain new fees such as the annual product fee and annual establishment fee which helped in pre-market evaluation. Few issues being raised in MDUFA II led the congress to enact an amendment. The next revision of the act made the review process more ef(cid:977)icient and interactive with the applicant to meet the timelines. Recent amendment has set up several new performance goals and propose certain changes to the previous amendments. The device manufacturers are currently in a position to receive regulatory approval in a short time compared to the pre-MDUFA period. MDUFA has helped in improving the patient health by streamlining the FDA’s approval process for application


INTRODUCTION
A medical device manufacturing agency should seek FDA approval before introducing the product in the US. The manufacturer may put the product onto the market in two ways, one by performing clinical studies and submitting an application for Pre-Market Approval (PMA) that provides proof that the device is safe to use and also effective; the other way is by submitting a 510(k) notice that the device is substantially equivalent to an existing device on the market and does not require a PMA. The Centre for Device and Radiological Health (CDRH) is primarily responsible for medical device premarket analysis within the FDA. The core purpose of the user fee is to support the medical device's PMA process by the FDA and to help reduce the time required to review and approve on the marketing request. A prolonged review time re lects both on the production industry as well as the consumer industry, who in this case is a patient. The policy on user fees offers FDA revenue. Negotiate quality targets for the premarket review of medical devices in exchange for the fees FDA and industry (FDA, 2016).
User fee funds is one of the revenue streams made available to the FDA to ful il its mandate to promote and protect public health by ensuring the safety and effectiveness of medical devices (Williams, 2010).
This guarantees that the patient receives safe and effective care more ef iciently and also ensures that the product being sold in the U.S continues to meet the high safety and ef icacy requirements (Mdufa and Pdufa, 2017).
Low-risk medical devices (Class I) and few moderate-risk medical devices (Class II) are excluded from pre-market review and fee payment (Dabrowska et al., 2017).
The user fee collection authority for medical devices is authorized in an expansion of ive years. According to the 2002 user fee rule, the fee to be paid by FDA alone was for the pre-market review, such as the PMA application fee, PMA supplement or noti ication 510(K). MDUFA II of 2007 established two forms of annual fees to create a more reliable revenue stream for the agency institution registration fees, charged by most FDA-registered device establishments, and consumer fees paid for highrisk devices (Class III) that require regular reporting. MDUFA III (2012) has changed the de inition of "registration fee establishment" increasing the number paying the fee. MDUFA I to III user fee is associated with pre market review of medical devices. MDUFA IV (2017) fee will fund medical device postmarket monitoring by collecting evidence from different sources in the real world.

Objective
The purpose of this study is to provide a review of the medical device user fee act and its amendments; to evaluate MDUFA's effect on the pharmaceutical industry.

Before MDUFA
In the years previous to the authorization of MDUFA, medical devices system of the FDA endured a long term, critical loss of asset that destabilized the programme's ability and execution. It was in mid-2002 that medical device industry and congress understood that the programme needed an extra asset. A few of the disadvantages that signalled the delay were -facilitated premarket approval application that were taking longer than standard review; delay in review because of lack of expertise, and most of the guidance documents went out-of-date. Therefore, the medical device industry's pioneers approached FDA and congress to start a discussion on new user fees and quicker product testing. Congress agreed that "FDA resources are limited, and it is possible that review times will increase in the future without a new in lux of funding. "Shortly afterwards, the Senate, the FDA and industry tried to develop a response; the 2002 Medical Device User Fee and Modernization Act (Mdufma On Background , 2017).

Medical Device User Fee and Modernization Act of 2002
MDUFMA was adopted in order to provide the FDA with the necessary resources for proper inspection of medical devices, to implement some regulatory changes so that medical device manufacturers can deliver safe and ef icient products to the American public sooner and to ensure that original and reprocessed medical devices are similar in the event of safety and ef icacy. MDUFMA has amended the Federal Food Drug and Cosmetics Act (FFDCA) to incorporate three important medical device requirement (Williams, 2010).
1. The user fee for the Pre-Market Analysis of devices has been created.
2. This allowed inspections by an approved individual to be carried out by the institution .
3. Introduced new regulatory requirements for reprocessed single-use products.

Progress under MDUFMA
The FDA has made signi icant progress in achieving the main goals of MDUFMA, 1. Research skills and expertise have been enhanced by hiring highly quali ied practitioners, improving staff training and establishing a fellowship program for medical devices.
2. Innovative review process available.
3. The FDA has set up a Combined Products Of ice to enhance the coordination of product reviews.
4. Enhance the review process by creating digital reporting and project management initiatives (Mdufma On Background , 2017). 2. The blockades in the third-party inspection program was removed.
3. The electronic labelling provisions were amended.
4. This postponed the execution of a clause requiring the product to bear the name of the manufacturer "principally and prominently" (FDA, 2016). Covering ive primary measures, 1. Reduced direct appropriation cause sums that were necessary for the company to receive user fees.
2. Revised the process of calculating user fee levels to reduce in lation, workload, compensation and inal-year revenue changes used to calculate charges.
3. The HHS Secretary was allowed to use noncompulsory balance sheets of the fees collected in previous iscal years.
4. It made registration and payment of reduced user fees simpler for small businesses.
5. Any reprocessed Single Use System (SUD) was deemed to be misbranded and therefore subject to FFDCA penalties if it did not identify the manufacturer but required such data to be provided by a detachable tag that was to be added to a

Medical Device User Fee Amendment II
Types of charges included in MDUFA II were the existing fees for reducing implementation prices, new annual supplier establishment fees, new annual consumer payments for on -the-market products. Such fees were used solely for pre-market evaluation and separate post-market surveillance appropriations.
According to the FDA, the quantity of applications submitted each year increased and decreased, and fee revenue consistently fell short of expectations.
In MDUFA 2007, there were two augmentations made to address the issues FDA was facing. It includes, establishment fee and product fee. Establishment fee was paid every year by an FDAregistered device establishment and product charge was charged for each Class III device for which PMA mandated periodic reporting each year. MDUFA 2007 helped to rise the total income produced by user fee by balancing the amount from applications with less application fee with revenue from the new fees (Mdufa and Pdufa, 2017).
Another issue addressed by MDUFA 2007 was that dissatisfaction with suitable issues for small business user fee discounts had been expressed by native and foreign companies.

Medical Device User Fee Amendment III
MDUFA III was the outcome of more than a year of public input and discussions with members of government, clinicians and customer (MDUFA III, 2017).
MDUFA III adjusts the total revenue by means of a prescribed in lation adjustment, similar to the changes made under PDUFA, and adjustments are made in the base fee amount as necessary on a uniform proportional basis to produce the total revenue adjusted for in lation. Upon adjusting the base fee amounts for in lation, the establishment fee amount is further adjusted as appropriate to produce the overall adjusted revenue amount from the total fee collections for the iscal year. The federal register consists of the current revised fee amounts and is published in the federal register 60 days before the beginning of each iscal year, together with the purpose for changing the fee amounts (FDA, 2016).

Process Improvements
Enhanced pre-submission process This process improved the predictability of FDA solutions for industry. The FDA has implemented a structured approach to address product-speci ic issues related to Pre-Market Approvals (PMA), 510(k)s and Exemptions for Experimental Devices (IDEs).

Submission Acceptance Criteria
FDA carried out revised submission acceptance standard through guidance to make the Pre-Market review procedure more ef icient.

Interactive Review
Informal communication among the FDA body of workers and device applicants helps to acquire suitable extra info and also helps in meeting assessment timelines.
Guidance Document Development MDUFA III user fee supports the development of guidance documents by the FDA, which are posted on the FDA website and represent the current questioning of the agency on the issue (Fact sheet, 2012).

Third-Party Review
The third-party review program involves a thirdparty reviewer who will conduct the primary review of 510(k) submission and then publish the review to FDA for the inal assessment. This program enhances the ef iciency and timelines of FDA's 510(k) review process for a speci ic device type

Emerging Diagnostics
The FDA will collaborate with industry under the MDUFA III program to develop a traditional approach to clinical technology regulation.

Medical Device User Fee Amendment IV
The MDUFA IV Agreement lays the foundation for further progress in FDA quality through more aggressive goals, substantial system changes and improved transparency, supported by additional resources (FDA User Fee Agreements, 2017).

MDUFA IV amended the Food, Drug and Cosmetics
Act on user fees earned on or after October 2017 for certain pre-market applications, including: 1. Pre market approvals (PMA).
2. Certain biologics license application that are considered devices.

Premarket noti ication submissions 510(k).
The FDA has committed itself to many new MDUFA IV performance targets, including, 1. issue MDUFA approval decisions requiring the input of the advisory committee within 60 days of the recommendation of the board.
2. make a de novo decision within 180 days or resolve all outstanding issues if no decision is reached within that period.
3. the de novo process permits approval of medical devices with low to moderate risk that lack a signi icantly comparable product on the market without applying a510(k) or PMA. Make a decision within 60 days following the sponsor's reaction to an accepted letter from MDUFA (Practical Law Life Sciences, 2017).

MDUFA IV Enhancements impact on User Fee Revenue
To order to enforce the MDUFA IV improvements, new funding is expected to be phased in during MDUFA IV. The new funding will be phased out as follows during each iscal year (FY).

Chart 4: New funding over each iscal year
The chart 4 will be adjusted for in lation each year, as prescribed below.

Proposed Statutory Changes
The draft proposals include the following proposed amendments to the Federal Food Drug and Cosmetics Act related parts to incorporate the existing MDUFA IV enhancements, Amend the premarket noti ication submission fee from 2 percent of the premarket application fee to 3.4 percent of the premarket application fee.
1. Modify the clause allowing small businesses to pay a reduced pre-market notice charge, increasing the payment from 50% of the standard fee to 25% of the standard fee.
2. Modify the charge for de novo identi ication applications equal to 30% of the pre-market application fee.
3. Change to re lect the requirement for a reduced fee for de novo classi ication applications submitted by a small business.
4. Modify to re lect that a reduced fee may be paid at 25% of the standard fee for a de novo classiication application.

Specify the amount of the base fee
For Pre market application Chart 5 shows the Base Fee amount for the Pre-Market Application.
Chart 5: Base fee amount for premarket application For Establishment Registration Chart 6 shows the Base Fee amount for Establishment Registration.
Chart 6: Base fee amount forestablishment registration Modify the allocation of in lation changes to the above-mentioned charges starting in FY 2016.
The proposed maximum statutory revenue amounts and base fee amounts are speci ied in (FY 2015) dollars so that annual in lation changes are used to in late (FY 2015) dollars to appropriate amounts based on actual in lation rates as de ined in the annual Federal Register Notice for each iscal year in MUDUFA IV.
Amend the fee setting process to re lect the negotiated agreement, where FDA is permitted to collect increased base fee amounts by not reducing the fee for larger submission and registrations. Further adjustments would be required only if the submissions and registrations are less than expected. In such cases, the base fee amount should be increased so as to produce the authorized total fee revenue in a given year.
Eliminate the ifth-year fee offset provision because the negotiated fee setting structure allows FDA to gather and utilize in lation adjusted base fee amounts each year with no decrease in fees due to increased submission or registration volume. Deleting the fee offset Provision is necessary to execute the negotiated fee setting structure.
Add a subsection to the provision on performance standards to provide power to FDA to establish a conformity assessment programme and to specify the requirements for establishing such program.
Amend the provision on accredited person to provide FDA authority to tailor the scope of the thirdparty review programme according to the contracts made with the regulated industry at the time of user fee reauthorization negotiation.
Amend the provision on electronic format for submission to provide FDA the authority to develop and implement electronic submissions according to the contracts made with the regulated industry at the time of user fee reauthorization negotiation. Some of the improvements in MDUFA III include progress in the evaluation process, structure and enhancement of ef iciency. MDUFA III incorpo-rated increased rigorous performance review targets and shared goals of the results. MDUFA III has been updated to accommodate improvements to the pre-market review process. MDUFA III will cover approximately 33% of the overall cost of the premarket review process for medicinal devices.

CONCLUSIONS
The annual drop-in approval times were limited after the MDUFA. During the MDUFA era (2003)(2004)(2005)(2006)(2007)(2008), as well as the period covered by the subsequent re-authorization of the law (2008-2012), this trend continued unabated, with data showing very small decline in device review times. The medical device fee was intended to provide stable and reliable funding for FDA with the need to reduce market entry barriers and encourage innovation. The fees aid in recruiting professional personnel, modernizing the information management process, promoting more communication between FDA and applicant, offering further advice to prospective applicants. Overall, these activities allow the FDA to review medical devices more ef iciently, reliably, regularly, and transparently for safety and ef icacy. It ultimately bene its distributors and suppliers, the culture of health care and, most importantly, the patients.
Williams, E. D. 2010. Medical Device User Fees and User Fee Acts. Specialist in Public Health and Bioethics.