Source: http://www.policymed.com/congress/
Timestamp: 2014-10-30 23:25:44
Document Index: 635201513

Matched Legal Cases: ['art 820', 'art 807', 'art 803', 'art 803', 'art 803', 'art 814', 'art 812', 'art 56', 'art 50', 'art 820', 'art 820', 'art 820']

Policy and Medicine: Congress
FDA to Propose Oversight of Laboratory Developed Tests
The U.S. Food and Drug Administration (FDA) has notified Congress that it intends to issue draft guidance to propose a risk-based, phased-in framework for oversight of laboratory developed tests (LDTs) and has provided the anticipated details of the LDT guidance in the notification. The notification sent on July 31 was required by the Food and Drug Administration Safety and Innovation Act (FDASIA), which requires notification to Congress at least 60 days prior to the issuance of draft or final guidance. Shift in FDA Policy Started in 2013 As reported by Regulatory Focus: FDA marked a shift in policy in 2013 when Commissioner Margaret Hamburg announced that FDA would be pursuing a regulatory framework for LDTs. "[FDA will be] working to make sure that the accuracy and clinical validity of high-risk tests are established before they come to market," Hamburg said. Hamburg said FDA was aware of the need to preserve an environment for innovation, and that it would be pursuing a risk-based framework to balance the need for evidence with innovation and patient access. But Hamburg's proposal received pushback from the LDT industry almost immediately. The American Clinical Laboratory Association (ACLA) filed a Citizen Petition with FDA arguing that the agency lacked the authority to regulate LDTs, which it said were regulated under the Clinical Laboratories Improvement Act (CLIA), which governs clinical laboratories and the standards they use to "assure consistent performance" and reliability. At the core of ACLA's argument is that it considers LDTs not to be devices, but rather procedures for performing diagnostic testing using reagents and equipment. FDA finally rejected that petition on July 31 and on the same day announced the release of its new LDT regulation policy. Overview According to a report by the law firm Morgan Lewis: FDA's risk-based approach will rely on the existing medical device classification system (Class I, II, or III) to evaluate the risk of a category of LDTs and, informed by the expressed interest in participating in the discussion of the classification process, will use expert advisory panels to help classify devices not previously classified by FDA. FDA intends to issue draft guidance to describe what it considers generally to be Class I, II, or III within 24 months of finalizing the LDT guidance. FDA anticipates that it will phase in enforcement of regulatory requirements for LDTs over the next 10 years. The phased-in enforcement for the different device categories is summarized in the following table, also created by Morgan Lewis: FDA Enforcement of Regulatory Requirements for Categories of LDTs—Time Frames
Low-risk devices, traditional LDTs, and LDTs for rare disease and unmet needs Enforcement discretion. Enforcement discretion. Enforcement discretion. Moderate-risk devices Six months after guidance is finalized. Phased-in enforcement will begin five years after guidance is finalized. FDA plans to announce priority list for class II within four years of finalized guidance.
Enforced once FDA issues a clearance order. High-risk devices Six months after guidance is finalized.
Phased-in enforcement will begin 12 months after guidance is finalized. FDA plans to announce priority list within 24 months of finalized guidance. Enforced once premarket approval application is submitted. Immediate Concerns Raised By American Medical Association
In a release from the Barbara L. McAneny, MD, Chairman of the Board at the American Medical Association, the organization expressed concern regarding the FDA proposal.
"The American Medical Association (AMA) believes that laboratory developed testing (LDT) services offer patients access to safe and high quality diagnostic services that are essential to patient care. "The draft FDA Framework for Oversight of Laboratory Developed Tests (LDTs) announced today, outlines a risk-based approach that raises a number of questions and concerns. "The FDA proposal adds an additional layer of regulatory requirements which may result in patients losing access to timely life-saving diagnostic services and hinder advancements in the practice of medicine. "The AMA is committed to ensuring that the proposal that is ultimately adopted by the FDA preserves rapid access to care and medical advancements." Association for Molecular Pathology
Additionally, the Association for Molecular Pathology (AMP) voiced concern with the proposal.
"Laboratory developed molecular pathology procedures have made enormous contributions to patient care in areas as diverse as oncology, infectious diseases, and inherited disorders. We are deeply concerned that attempts to regulate providers of these vital medical services as manufacturers, will harm patients by reducing access, decreasing innovation, and substantially raising the costs of essential diagnostic testing," said Roger Klein, Chair of the Professional Relations Committee at AMP. AMP recently published an updated position statement on the regulation of LDPs and believes that the current oversight mechanisms already in place are sufficient for the majority of tests currently in practice. Moreover, LDPs are often the standard-of-care, the highest quality test available, and at times, the only available testing option.
Congressman Burgess, vice chairman of the House Energy and Commerce Subcommittee on Health, responded to the FDA notification to Congress that it will release draft guidance to regulate LDTs with the following statement:
"Applying FDA's regulatory approach to LDTs is redundant, will stifle innovation and will require additional taxpayer funding for the FDA. To the extent concerns about 'higher-risk' tests exist; these can be addressed at no cost to the government through a modernization of The Clinical Laboratory Improvement Amendments (CLIA). "Given the negative impact these policies – if pursued – could have on innovation, I am glad I was able to secure this notification requirement within the Food and Drug Administration Safety and Innovation Act of 2012. LDTs are not medical device products sold through interstate commerce. They are services provided only to the ordering healthcare provider and offered only by labs that validate and develop them. Professional medical services are not regulated by FDA. More importantly, the question of agency jurisdiction over LDTs has never been legally clarified. LDTs neither constitute "medical devices" nor are commercially distributed among states – both requirements for FDA jurisdiction under the Federal Food, Drug, and Cosmetic Act (FFDCA).
"FDA is the subject of much criticism from industry groups who are already under their jurisdiction. As such, they are overburdened and take too long to approve products, which increases uncertainty for companies and negatively impacts innovation, as well as patient access to new treatments and devices. If LDTs were regulated as medical devices by FDA, it would significantly tax an already overtaxed agency and stifle access to these important tests.
"The Energy & Commerce Committee is continuing to develop the 21st Century Cures initiative and explore how we can encourage innovation. We are also looking into ways to increase our ability to detect, treat and cure disease. I fear today's move by the FDA moves in the opposite direction and I look forward to raising this issue often in the coming months."
We will continue to follow this story on Policy and Medicine in the months to come.
I. LDT Guidance Overview
A. Defining LDT and Scope of Guidance FDA defines the term laboratory developed test (LDT) as an IVD that is intended for clinical use and designed, manufactured and used within a single laboratory. The following is an example of an LDT: A laboratory uses peer reviewed articles to guide development of a new diagnostic device. The laboratory uses general purpose reagents and analyte specific reagents combined with general laboratory instruments and develops a testing protocol, that together constitute a test system which is then verified and validated within the laboratory. Once validated this device is used by the laboratory to provide clinical diagnostic results. FDA does not consider devices to be LDTs if they are designed or manufactured completely, or partly, outside of the laboratory that offers and uses them. The following are some examples of devices that FDA does not consider to meet the definition of an LDT: An entity that owns several clinical laboratories develops a device in one of its clinical laboratories and then transfers the device to several clinical laboratories within its network. An academic institution develops a device, which it then licenses to or signs an exclusivity agreement with a private corporation that owns a CLIA-certified laboratory. The private corporation's CLIA-certified laboratory then begins manufacturing and using the device to provide clinical diagnostic results. A laboratory contracts with a third party manufacturer to produce a key component (e.g., coated microtiter plate, specialized specimen collection kit) used in its device. A laboratory contracts with a specification developer to design a new device. Once complete, the design is then transferred to the clinical laboratory for final validation prior to the device being manufactured and used by the laboratory to provide clinical diagnostic results. B. Risk-Based Approach toward Oversight of LDTs FDA believes it should no longer generally exercise enforcement discretion towards all LDTs. Once finalized and implemented, this guidance document is intended to provide an oversight framework that will assure that devices used in the provision of health care, whether developed by a laboratory or a conventional IVD manufacturer, comply with the appropriate levels of regulatory controls. i. Risk-Based Classification Medical devices are classified as Class I, II or III based upon the controls necessary to provide a reasonable assurance of the safety and effectiveness of the device, and factors relevant to this determination include the device's intended use, technological characteristics, and the risk to patients if the device were to fail. Class I devices, which are subject only to general controls, generally represent the lowest-risk category of devices, while Class III devices, which are subject to general controls and premarket approval, generally represent the highest-risk devices. Section 513(a)(1) of the FD&C Act (21 U.S.C. 360c(a)(1)). FDA will rely upon the existing medical device classification system to evaluate the risk of a category of LDTs and, informed by the industry's expressed interest in participating in the discussion of the classification process, will use expert advisory panels to help classify devices not previously classified by FDA, as appropriate. In determining the risk an LDT poses to the patient and/or the user, FDA will consider several factors including whether the device is intended for use in high risk disease/conditions or patient populations, whether the device is used for screening or diagnosis, the nature of the clinical decision that will be made based on the test result, whether a physician/pathologist would have other information about the patient to assist in making a clinical decision (in addition to the LDT result), alternative diagnostic and treatment options available to the patient, the potential consequences/impact of erroneous results, number and type of adverse events associated with the device, etc. To provide additional clarity, FDA intends to issue draft guidance to describe what the Agency considers generally to be Class I, II or III within 18 months of finalization of this guidance. ii. LDT Framework FDA intends to continue to exercise enforcement discretion for all applicable regulatory requirements for: LDTs used solely for forensic (law enforcement) purposes. Certain LDTs for transplantation when used in CLIA-certified, high-complexity histocompatibility laboratories. FDA intends to exercise enforcement discretion for applicable premarket review requirements and quality systems requirements, but enforce other applicable regulatory requirements including registration and listing (with the option to provide notification) and adverse event reporting, for: Low-risk LDTs (Class I devices). LDTs for rare diseases and "Traditional LDTs."16 These types of LDTs reflect the types of LDTs that existed when the enforcement discretion policy was initially implemented. "LDTs for Unmet Needs," when no FDA-approved or cleared equivalent device is available. For other high and moderate risk LDTs, FDA intends to enforce applicable regulatory requirements, including registration and listing (with the option to instead provide notification), adverse event reporting, premarket review, and quality system requirements, as follows: High-risk LDTs (Class III medical devices): Registration and listing (with the option to provide notification) and adverse event reporting begin six months after this guidance is finalized. Premarket review requirements begin 12 months after this guidance is finalized for the highest risk devices and phase-in over 4 years for the remaining high-risk devices. Devices would remain on the market during review and FDA's consideration of applications. FDA's focus on high-risk devices begins with the following: a) LDTs with the same intended use as a cleared or approved companion diagnostic; b) LDTs with the same intended use as an FDA-approved Class III medical device; and c) certain LDTs for determining the safety or efficacy of blood or blood products. Moderate-risk LDTs (Class II medical devices): Registration and listing (with the option to provide notification) and adverse event reporting begin six months after this guidance is finalized. Premarket review requirements begin after the high-risk (Class III) LDTs are completed, meaning 5 years after the guidance is finalized, and phase- in over 4 years. FDA intends to utilize FDA-accredited third party review of premarket submissions as appropriate. Where an LDT's analytes/markers that are measured/assessed have had their clinical validity already established in the literature, FDA believes it may not be necessary for sponsors to conduct extensive new studies to demonstrate clinical validity of the analytes/markers, but the sponsor will need to demonstrate that any changes in technology or methodology that differ from that used in the literature to assess the analyte/marker do not affect the clinical validity of the LDT. FDA intends to work with the laboratory community, the health care professional community, and other stakeholders to identify those LDTs for which the clinical validity of the analyte/marker has already been established in the literature. In addition, for those LDTs that present moderate risk, FDA intends to work with interested parties to expand the Agency's third party review program to include these types of devices. If successful, FDA believes that most moderate-risk LDTs could be reviewed by a third party reviewer. Under this model, FDA would generally review high-risk LDTs subject to a premarket approval application (PMA) (i.e., Class III medical devices), while accrediting third parties to carry out review of most moderate-risk LDTs requiring a premarket notification (510(k)) submission (generally Class II devices). FDA intends to continue exercising enforcement discretion with respect to applicable premarket review requirements and quality system requirements for Class I devices, which present the lowest risk. iii. Timeline Registration and Listing/Notification and Adverse Reporting: Six months after this guidance becomes final, manufacturers of LDTs should notify FDA if they are developing LDTs and must begin to report significant adverse events to FDA, so that problems can be detected and corrected in a timely manner. Premarket Review: FDA intends to phase-in enforcement of premarket review requirements for relevant LDTs over an extended period of time. LDT categories will be phased-in for enforcement based on risk, and the number and type phased-in at a given time will be commensurate with available agency resources. The phased-in enforcement, starting with the highest-risk, will begin 12 months after the guidance becomes final. FDA will prioritize all other LDTs based on risk using a public process, including expert advisory panels as appropriate, and will provide advanced notice with respect to timing of enforcement to manufacturers of LDTs that fall into the high- and moderate- risk categories. Premarket review for the highest risk devices will begin 12 months after this guidance is finalized. FDA expects to announce the priority list for the remaining high-risk devices within 24 months from finalization of the guidance, with enforcement for the initial prioritized group on this list of LDTs beginning no less than 12 months after the announcement of the priority list. FDA intends to complete phased-in enforcement of premarket review requirements for Class III devices first (within a period of 5 years of finalization of the guidance). FDA intends to phase in enforcement of requirements for Class II devices once FDA has completed the phase-in of the Class III devices. FDA expects to announce the prioritization of moderate-risk devices within 4 years of finalization of the guidance and complete phased-in enforcement of premarket regulatory requirements for Class II devices within 9 years of finalization of the guidance. Under the proposed framework, laboratories that manufacture LDTs would comply with appropriate quality controls in the FDA QS reg (21 CFR Part 820) when a PMA is submitted or FDA issues a 510(k) clearance order for the LDT. II. Framework for Regulatory Oversight of LDTs The framework for regulatory oversight of LDTs discussed below describes FDA's general enforcement priorities for LDTs. As a general matter, FDA proposes a risk-based, phased-in approach, in combination with continued exercise of enforcement discretion for certain regulatory requirements and certain types of LDTs. A. Main elements The main elements of FDA's framework for regulatory oversight include: Either notification to FDA of LDTs manufactured by a laboratory or Registration and Listing Medical Device Reporting Requirements (MDR) for LDTs (e.g., adverse event reporting) Continued enforcement discretion with respect to premarket review requirements for low-risk LDTs, "Traditional LDTs," LDTs used for rare diseases, and "LDTs for Unmet Needs" Risk-based, phased-in approach to enforcing the premarket review requirements for other high-risk and moderate-risk LDTs Use of clinical literature to support a demonstration of clinical validity, which FDA expects would reduce the need for additional clinical studies to show clinical validity for LDTs where the analytes/markers that are measured/assessed have had their clinical validity established in the literature Facilitation of third-party review for many moderate risk LDTs Phased-in approach to enforcing the Quality System regulation Continued enforcement discretion for premarket review of Class I LDTs For those LDTs that are already FDA approved or cleared, it is FDA's expectation that manufacturers will continue to follow the regulations. Manufacturers of tests that are used solely for in-process quality control testing in the manufacture of FDA-regulated articles should consult with FDA to determine applicable regulatory requirements. B. Continued Enforcement Discretion in Full for Certain Categories of LDTs FDA intends to continue to exercise enforcement discretion in full for certain categories of diagnostic devices. For the following devices, FDA does not intend to enforce applicable registration and listing (nor is FDA requesting notification), adverse event reporting, premarket review, or quality system requirements: (a) LDTs Used Solely for Forensic (Law Enforcement) Purposes; (b) LDTs Used in CLIA-Certified, High-Complexity Histocompatibility Laboratories for Transplantation. C. Notification to FDA of LDTs Manufactured by a Laboratory or Registration and Listing With the exception of the categories of devices identified above in (forensic (law enforcement) LDTs and certain LDTs used in connection with organ, stem cell, and tissue transplantation), for laboratories that manufacture, prepare, propagate, compound, assemble, or process LDTs, FDA intends to continue to exercise enforcement discretion with respect to registration and listing requirements (21 CFR Part 807) provided that such laboratories notify FDA that they are manufacturing LDTs and provide basic information regarding each of these LDTs. Notification is expected to occur once for each LDT, although if significant changes are made to an LDT, additional notification should be provided. Laboratories should provide notification information to the FDA within 6 months of the date of publication of the final version of this guidance document with respect to their LDTs on the market on the date of publication of the final version of this guidance document, and any new LDTs on the market in the 6 months following publication of this document. Starting 6 months after publication of the final version of this guidance, laboratories offering new LDTs should provide notification prior to offering the LDT for clinical use. It should be noted that when a laboratory makes a significant change to the marketed intended use of an LDT for which they have previously provided notification, the LDT will be considered by the FDA to be a new LDT. Therefore, a new notification should be provided prior to offering that LDT for clinical use; this is especially important for those changes in marketed intended use that increase the risk of the device. Additionally, following initial notification, FDA urges laboratories that make other significant modifications to LDTs after notification to re-submit notification data to FDA to communicate such changes of the guidance for additional information on significant device modifications). Given that notification data will be used to classify LDTs and prioritize enforcement of premarket review requirements based on risk, it will benefit laboratories to provide the most accurate information possible to ensure that appropriate classification is made. D. Medical Device Reporting (MDR) Requirements With the exception of the categories of tests identified above (forensic (law enforcement) LDTs and certain LDTs used in connection with organ, stem cell, and tissue transplantation), FDA intends to enforce the manufacturer reporting requirements of the Medical Device Reporting (MDR) regulation (21 CFR Part 803, Subpart E) for laboratories manufacturing LDTs. The MDR regulation requires the manufacturer of a medical device to submit reports to the FDA whenever they become aware of information that reasonably suggests that a device they market may have caused or contributed to a death or serious injury, or has malfunctioned and the malfunction would be likely to cause or contribute to a reportable death or serious injury should it recur. (21 CFR 803.50.) One objective of the MDR regulation is to provide a mechanism for FDA and device manufacturers to identify and monitor significant adverse events involving medical devices so that problems may be detected and corrected in a timely manner. This information is particularly important in the case of LDTs, as many of these devices have not undergone premarket review. MDR reporting for LDTs will provide for an important risk mitigation measure to detect, track, and help address serious problems related to LDT performance should they occur. Therefore, beginning six months following publication of the final version of this guidance document, FDA intends to cease its exercise of enforcement discretion with respect to the MDR reporting requirements in 21 CFR Part 803, Subpart E, for laboratories that manufacture LDTs. A description of the specific requirements in 21 CFR Part 803, Subpart E, as well as further information on how the MDR requirements apply to laboratories is described in the guidance document "FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)." E. Premarket Review Requirements With the exception of the categories of devices identified above (forensic (law enforcement) LDTs and certain LDTs used in connection with organ, stem cell, and tissue transplantation) and those otherwise identified, FDA intends to phase in the enforcement of applicable premarket requirements over time based upon the risk associated with that device. FDA intends to focus its efforts on the highest risk devices first and gradually phase in enforcement for other devices over time. In this manner, it is FDA's intention to avoid undue disruption of medical testing while seeking to assure patient safety and to assure that health care practitioners are relying on device results that are meaningful and accurate when making medical decisions. i. Continued Enforcement Discretion with Respect to Premarket Review Requirements for LDTs Used for Rare Diseases and "Traditional LDTs" The FDA believes that it is appropriate to continue to exercise enforcement discretion with respect to premarket review requirements for the two categories of LDTs described below. (a) LDTs Used for Rare Diseases The Humanitarian Use Devices (HUD)/Humanitarian Device Exemption (HDE) provisions of the Act (21 U.S.C. 360j(m)) and regulations (21 CFR 814, Subpart H) provide an abbreviated regulatory pathway as an incentive for the development of devices for use in the treatment or diagnosis of rare diseases or conditions. FDA recognizes that some LDTs may qualify as HUDs. An IVD device may qualify for HUD designation when the number of persons who may be tested with the device is fewer than 4,000 per year. FDA recognizes that one patient may be tested multiple times with the same device; when this occurs, the multiple uses are counted as one use for purposes of defining which devices may qualify as HUDs. If an IVD is being developed to diagnose or to help diagnose a disease or condition with an incidence of fewer than 4,000 patients per year, but there are more than 4,000 patients a year who would be subject to testing using the device, then the device does not qualify as a HUD (21 CFR 814.102(a)(5)). While FDA encourages laboratories manufacturing LDTs for rare diseases to seek approval under the HDE provisions, FDA plans to continue to exercise enforcement discretion with regard to premarket review requirements for LDTs that meet the definition in this guidance and the definition of an HUD under 21 CFR 814.102(a)(5). (b) Traditional LDTs FDA intends to continue to exercise enforcement discretion with respect to premarket review requirements for "Traditional LDTs," which are those IVD devices that reflect the types of LDT available when FDA began its policy of generally exercising enforcement discretion over LDTs in 1976. In considering whether to exercise enforcement discretion for Traditional LDTs, FDA intends to consider the following factors: (1) Whether the device meets the definition of LDT in this guidance (a device designed, manufactured and used by a single laboratory); and (2) Whether the LDT is both manufactured and used by a health care facility laboratory (such as one located in a hospital or clinic) for a patient that is being diagnosed and/or treated at that same health care facility or within the facility's healthcare system; and (3) Whether the LDT is comprised of only legally marketed components and instruments (e.g., analyte specific reagents (21 CFR 864.4020), general purpose reagents (21 CFR 864.4010), and various classified instruments); and (4) Whether the LDT is interpreted by qualified laboratory professionals, without the use of automated instrumentation or software for interpretation. ii, Continued Enforcement Discretion with Respect to Premarket Review Requirements for "LDTs for Unmet Needs" When No FDA-cleared or -approved Alternative Exists FDA recognizes the role that LDTs can play in meeting urgent unmet healthcare needs. FDA believes it is important to maintain the availability of LDTs that serve unmet needs (but that are not LDTs for rare diseases or "Traditional LDTs") until a comparable FDA-cleared or -approved device becomes available. For this reason, FDA intends to exercise enforcement discretion with respect to premarket review requirements for "LDTs for Unmet Needs." In determining whether an LDT is an "LDT for Unmet Needs," FDA intends to consider the following factors: (1) Whether the device meets the definition of LDT in this guidance (a device designed, manufactured and used by a single laboratory); and (2) Whether there is no FDA cleared or approved IVD available for that specific intended use; and (3) Whether the LDT is both manufactured and used by a health care facility laboratory (such as one located in a hospital or clinic) for a patient that is being diagnosed and/or treated at that same health care facility or within that facility's healthcare system. For LDTs for Unmet Needs, FDA does not intend to consider factors such as whether the LDT is comprised of only legally marketed components and instruments or whether the LDT is interpreted by qualified laboratory professionals, without the use of automated instrumentation or software for interpretation. FDA believes that greater flexibility is appropriate for LDTs for Unmet Needs because there is no FDA-cleared or approved alternative for the device on the market. iii. Enforcement of Premarket Submission Requirements for Companion Diagnostics and Other High-risk Diagnostic Device Category LDTs FDA intends to initially focus its enforcement priorities by generally enforcing the premarket review requirements beginning 12 months after this guidance is finalized for the following LDTs: a) LDTs with the same intended use as a cleared or approved companion diagnostic; b) LDTs with the same intended use as an FDA-approved Class III medical device; and c) certain LDTs for determining the safety or efficacy of blood or blood products. FDA believes that these diagnostic device categories are among the highest risk LDTs currently available on the market because the device either is used to direct patient therapy (as in the case of LDTs with the same intended use as a cleared or approved companion diagnostic) or has the same intended use as a device that FDA has already determined to be in the highest risk classification (Class III). For 12 months following publication of this guidance document in final form, FDA intends to exercise enforcement discretion with respect to premarket review requirements for currently marketed LDTs. FDA intends to begin enforcing premarket review requirements for these categories of currently marketed LDTs at the end of that 12-month period. If the appropriate premarket submission (generally a PMA) is made within the 12-month period, FDA intends to continue to exercise enforcement discretion while the premarket submission is under FDA review, so as not to interrupt patient access. FDA intends to begin enforcing premarket review requirements immediately upon publication of this guidance document in final form for all new LDTs (i.e., those that become available for patient testing after final publication of this guidance document) in these categories. FDA will expect manufacturers of these new LDTs to make an appropriate premarket submission and obtain approval or clearance for their devices prior to use. iv. Phased-In Enforcement of Premarket Requirements for Other LDT Categories After FDA collects and analyzes notification data, it will prioritize the remaining device categories based on risk using a public process. FDA plans to utilize advisory panels to provide recommendations to the Agency on LDT risks and prioritization of enforcement of applicable regulatory requirements on certain categories of LDTs, as appropriate. FDA intends for there to be ample opportunity for public comment. v. Modifications to FDA Cleared/Approved Devices As in the case of any other entity, a clinical laboratory that modifies an FDA cleared/approved device in a way that affects device performance or intended use is considered to be a device remanufacturer (21 CFR 820.3(w)). Such modifications may include change in specimen type or sample matrix (e.g., saliva vs. whole blood), type of analysis performed (e.g., qualitative vs. quantitative), the purpose of the assay (e.g. screening, diagnosis, prognosis, monitoring, surveillance, and confirmation), the target population(s), etc. These modified devices must meet premarket submission requirements under 21 CFR 807.81(a)(3) and 21 CFR Part 814. FDA intends to begin enforcing premarket requirements for these modified devices as the Agency begins enforcing premarket requirements for the LDT category under which the modified device falls. vi. Clinical Investigations FDA intends to continue to enforce investigational device requirements under 21 CFR Part 812 for all clinical investigations of LDTs that are conducted under clinical protocols that require institutional review board approval. Before conducting an investigation, clinical laboratories must follow applicable requirements in 21 CFR Part 56 for institutional review board (IRB) approval as well as applicable requirements in 21 CFR Part 50 for informed consent from the study subjects at the time of their enrollment in the study. vii. Evaluation of Clinical Validity of LDTs FDA expects that for many LDTs, clinical validity has already been established in literature. FDA emphasizes that it is the Agency's practice to leverage such information from the literature in lieu of requiring additional studies to demonstrate clinical validity. In these cases FDA may still require studies demonstrating device performance (e.g., analytical evaluations) but generally intends to rely on the scientific literature to support clinical validity if appropriate. FDA intends to work with the laboratory community, the healthcare professional community and other stakeholders to determine whether an LDT's clinical validity has already been established in the literature. viii. Third Party Review For LDTs, FDA envisions that the Agency would generally review PMAs for high- risk (Class III) LDTs, whereas third parties would generally review the 510(k)s for lower risk (Class II) LDTs. FDA seeks to work with interested parties that have experience with laboratories and can meet FDA requirements for third party reviewers. FDA anticipates that inclusion of such groups will facilitate a more efficient review process for LDTs. If this approach is successful, most 510(k)s for LDTs could be reviewed by appropriate third parties. F. Quality System Regulation Requirements The Quality System Regulation (21 CFR Part 820) was developed to define the minimal quality system requirements that medical device manufacturers must implement in order to assure that the finished device will be safe and effective. FDA intends to continue to exercise enforcement discretion with respect to QS reg requirements, codified in 21 CFR Part 820, until a manufacturer of a given LDT submits a PMA or FDA issues a 510(k) clearance order for the LDT. Under this enforcement policy, the clinical laboratory manufacturing and using the LDT will be responsible for having a quality system in place that meets the minimum requirements codified in 21 CFR Part 820, either at the time of PMA submission (the facility that makes the device must pass an inspection as a condition of PMA approval as a matter of law (21 CFR 814.45(a)(3))), or prior to market launch for cleared devices, as applicable. This initial period of continued exercise of enforcement discretion for QS reg requirements is intended to allow time for laboratories to learn about their regulatory obligations under the Act, as well as to develop programs to comply with them. FDA intends to assist laboratories in understanding these and other applicable requirements prior to enforcing those requirements.
Posted by Thomas Sullivan on August 04, 2014 at 05:35 AM in Congress, FDA | Permalink
In May, Senator Lamar Alexander (R-TN), the ranking member of the Senate HELP Committee, along with Senators Richard Burr (R-NC), Johnny Isakson (R-GA), and Orrin Hatch (R-UT), sent a letter to FDA Commissioner Margaret Hamburg "to express significant concern about [FDA's] use of draft guidances to make substantive policy changes." The letter notes that draft guidances are becoming default FDA policy, notwithstanding that they are issued for comment purposes only. Moreover, draft guidances are not revised, finalized, or withdrawn in a timely manner. Additionally, as previously reported, draft guidances often are the only information that the medical community, FDA-regulated entities, and FDA review staff may have on the agency's current position on important issues. Stakeholders feel constrained by the policy positions laid out in draft guidance, even (or perhaps especially) when those positions are inconsistent with consensus within the biomedical community-a fourth concern of the senators. In its September 2012 Report to the President On Propelling Innovation In Drug Discovery, Development, and Evaluation, the President's Council of Advisors on Science and Technology (PCAST) recommended, among other things, that the FDA rely on-and reflect the consensus of-the scientific community in developing and revising guidances. Despite this recommendation, however, the senators cited recent draft guidances by the FDA that did not incorporate recommendations by the international scientific community. The letter requests FDA to respond to the following information requests and questions: 1. A list of all Level I Draft Guidances, including the date issued, and the timeline with which you plan to withdraw, revise, or finalize each guidance. 2. An update on Agency-wide activities to implement the "best practices" to make the finalization of guidance more efficient and expeditious, as discussed in the 2011 report Food and Drug Administration Report on Good Guidance Practices: Improving Efficiency and Transparency. 3. Have you implemented the President's Council of Advisors on Science and Technology recommendation to rely more on the biomedical community in help developing and revising guidances, and if so, could you provide examples of specific guidances? 4. For the guidances still in draft form, how do you ensure your staff does not follow the guidance in the absence of any other policy or final guidance? 5. What is the average amount of time in calendar days that the FDA has taken to finalize draft guidances in the last five years? What is the range? Because these are all minority members on the HELP committee it will be interesting to see if the FDA ever responded to their requests. Posted by Thomas Sullivan on July 31, 2014 at 05:02 AM in Academic Organizations, Congress, FDA | Permalink
The 21st Century Cures initiative is a new bipartisan effort to bridge the gap between medical advances and the regulatory policies that govern them. The initiative started with a collaboration between Representative Fred Upton (R–MI), the chair of the Energy and Commerce Committee, and Representative Diana DeGette (D–CO), one of the panel's senior Democrats. The initiative aims to examine the "full arc" of the innovation process to get new treatments and cures to patients more quickly. The committee hopes to streamline the drug and device development process, and "unleash[] the power of digital medicine and social media" in the treatment delivery phase. In an article co-authored by Upton and Degette discussing their vision, the lawmakers stated: "There should be no gap between 21st century science and the Washington regulatory process." Groundbreaking medical breakthroughs have the potential to redefine patient care. For example, "granular-level biochemistry," Upton notes, has the potential "to take early detection to a whole new level, identifying and treating defective genetic structures even before they produce clinical symptoms." Furthermore, advances in technology and social media allow an amazing level of connectivity between patients, doctors, and scientists. "The revolution in molecular biology, computing power and social networks demands that we take a fresh look at our drug approval regime and make sure it is taking advantage of all these new tools," Upton argues. Health research is moving quickly, "but the federal drug and device approval apparatus is in many ways the relic of another era." Degette states, "when our laws don't keep pace with innovation, we all lose." Recent Activity
In the time since the initiative was announced April 30th, the Committee has released several whitepapers and hosted roundtable discussions and hearings focused on how best to accelerate the pace of cures in America. Most recently, the Committee released a digital health white paper and on June 24th, held a roundtable discussion about leveraging technology to accelerate the discovery, development, and delivery cycle of new cures. Upton and his committee believe technology holds great potential to help healthcare evolve. "As we work toward a path to cures," Upton states, "we must always be improving and evolving, embracing the technologies of today as we pursue the treatments for tomorrow." The roundtable included industry experts, doctors, and CEOs, who discussed the commercial and regulatory barriers that prevent healthcare technologies from being used on a larger scale in the treatment process. "First and foremost," Dr. Jeff Shuren, Director of the Center for Devices and Radiological Health at the FDA states is the importance of "accurate information." When technology analyzes patient information on a large scale, in order to be beneficial to patients, the information must be correct. Another major obstacle is the "lack of interoperability and sharing of health information," notes Joseph M. Smith, M.D., chief medical and science officer at West Health. Current business models keep everything separate. Smith wants a "seamless flow of information at the point of care." The idea is that communities of people online, along with companies with molecular and genetic databases, can help target, contact, and monitor people much more efficiently than the current clinical trial process. Dr. Brian Druker, director of the Oregon Health and Science University's Knight Cancer Center, states that he envisions in the not too distant future a cancer patient who is able to benefit from a "million cancer patients before them" through the use of technology. In addition to utilizing "big data," a major them of the roundtable was patient involvement in their own healthcare. Technology can help. Fierce HealthIT noted that panelists "touted the importance of consumer control over their own healthcare information." Anne Wojcicki, co-founder of DNA-analysis company 23andMe stated: "For the first time, technology and healthcare are coming together and consumers want to be part of it." Interestingly, late last year, 23andMe received a Warning Letter from FDA, ordering it to stop marketing its saliva kits for personal genome testing. Upton took issue to this in an article earlier this year: "Again, today's FDA seems less than open to these new tools. Instead of welcoming innovators like 23andMe – a company that seeks to empower individuals by supplying them with individualized health information – the FDA has shut down one of the company's key offerings." Mark Blatt, the Worldwide Medical Director of Intel Corporation, spoke about the OpenNotes program, adopted by some healthcare facilities, including the Cleveland Clinic. Blatt used the program as an example of how patients can have access to their healthcare information. OpenNotes gives patients access to the visit notes written by their doctors. It's a free technology that encourages patients to directly get involved in their healthcare, Blatt said.
The Committee also discussed how patient privacy may be affected by data analysis and how to address privacy concerns and informed consent to data collection. The committee said it wants to create a regulatory framework that not only keeps privacy at the forefront, but also allows development and innovation when it comes to treatments and cures for patients. A number of speakers noted that HIPAA may be "protecting patients to death." Martin Harris, CIO of the Cleveland Clinic, spoke about HIPAA compliance, saying there should be general regulation of the program that empowers a patient to opt out. Economic and Regulatory Incentives for Cures Earlier this month, the House Energy and Commerce Health Subcommittee convened for a hearing focused on the role of incentives in advancing treatments and cures, and whether current economic and regulatory incentives are sufficient to encourage robust research and development investment for innovative drugs and medical devices. Upton summarized three main points he hopes the 21st Century Cures initiative will address: (1) he would like to see overall decreases in time and cost for the FDA process of approval; (2) he is in favor of extending patent exclusivity and a review of Hatch-Waxman; (3) he encouraged the refinement of the coverage and reimbursement process for medical devices in order to spur innovation.
Posted by Thomas Sullivan on July 09, 2014 at 05:06 AM in Congress, Innovation | Permalink
FDA: House Republicans Question Generic Drug Rulemaking Process
A large group of House Republicans is once against raising questions about the U.S. Food and Drug Administration's (FDA) development of a rule that would change the way generic drug labels are regulated, saying it has "significant questions" about the involvement of a group of trial lawyers in the process and is interested in proposing its own "alternative approaches." As explained by Regulatory Focus, the FDA's meetings related to the development of the rule has drawn criticism from Republican legislators due to the possible influence of trial lawyers on the FDA's decision-making. This is in large part because of FDA's apparent violation of Executive Order 13563, which regulates how the executive branch is supposed to manage public participation. That order reads in part: "Regulations shall be adopted through a process that involves public participation. To that end, regulations shall be based on the extend feasible and consistent with law, on the open exchange of information and perspectives among State, local and tribal officials, experts in relevant disciplines, affected stakeholders in the private sector, and the public as a whole. … Before issuing a notice of proposed rulemaking, each agency, where feasible and appropriate, shall seek the views of those who are likely to be affected, including those who are likely to benefit from and those who are potentially subject to such rulemaking." The problem, according to lawmakers, is that FDA apparently did not meet with anyone from the generic drug industry, which stands to be affected most by the proposed rule, yet ultimately had no input during its development. In a new letter to FDA, Republican legislators said it is "not at all clear why plaintiffs lawyers would have any role in the development and review of the proposed rule." The legislators cited FDA's own past statements indicating that it has a vested interest in maintaining its sole status as "gatekeeper" in the labeling process. "We share these longstanding views, and in fact are very concerned that the result of this proposed rule would be therapeutically equivalent products with different warnings and contraindications based on companies taking actions to mitigate litigation risks-not based on communicating genuinely new risks to patients," the legislators wrote. Legislators asked FDA to turn over all documents, communications and meeting minutes related to its 15 February meeting with the AAJ and other trial attorneys, presumably to see if points raised by the attorneys made their way into the rule or otherwise influenced FDA's thinking. The letter goes on to state that legislators are interested in opening a "dialogue" with FDA on the "timeframes by which generic manufacturers must make conforming changes to ensure consistency," and opening up further discussions on "alternative approaches" to regulating generic drug labels "consistent with the statute." While never saying so explicitly, it would appear that legislators have formulated one or more alternatives to FDA's proposed rule and are prepared to play hardball to get the agency to back off.
Posted by Thomas Sullivan on June 23, 2014 at 05:21 AM in Congress, FDA | Permalink
Continuing Medical Education Legislative Activity
Within the last few months, legislators from across the country have introduced bills that involve Continuing Medical Education (CME). In this article we looked at three in particular that focus on separate areas of healthcare: nutrition, controlled substances, and Veterans Affairs. Education and Training for Health Act of 2014(H.R. 4378), introduced April 2, 2014 The Education and Training (EAT) for Health Act of 2014 seeks to require 6 hours of continuing medical education (CME) on nutrition for physicians employed by the federal government. The bill, introduced by Rep. Raul Grijalva (D-Ariz) and co-sponsored by Rep. Tim Ryan (D-Ohio) on April 2nd, encourages a stronger focus on nutrition and disease prevention in medical education. The bill was referred to the Committee on Energy and Commerce. The EAT for Health Act of 2014 notes that a large percentage of chronic diseases such as heart disease, cancer, and diabetes can be prevented and treated by proper nutrition and other lifestyle changes. Medical education is an important step towards that goal. In 2004, 38 percent of medical schools required 25 hours of nutrition education as part of their curriculum. By 2010, that number had shrunk to 27 percent. Furthermore, "[a]ccording to the Journal of the American College of Nutrition, physicians feel inadequately trained to provide proper nutrition advice. Ninety-four percent feel nutrition counseling should be included during primary care visits, but only 14 percent felt adequately trained to provide such counseling." "Changes in public policy are necessary to ensure physicians who are employed by the federal government are kept up-to-date on changing nutrition standards," states the Eat for Health Act Fact Sheet. The final version of the Act proposed the following requirements: "Not later than 180 days after the date of the enactment of this Act, the Secretary of Health and Human Services shall issue guidelines to Federal agencies for developing procedures and requirements to ensure that every primary care health professional employed full-time for such agencies have at least 6 credits of continuing medical education courses relating to nutrition." The Act states that continuing medical education relating to nutrition should include "courses on the role of nutrition in the prevention, management, and, as possible, reversal of obesity, cardiovascular disease, diabetes, and cancer." The Act also requires that the head of each Federal agency that employs full-time primary care health professionals submit to Congress a report attesting to the extent to which the agency has adopted and enforced the guidelines. "This isn't just about keeping medical costs down, although that's an important goal," Rep. Grijalva states on is website. "More than anything, it's about making sure Americans get the best advice about healthy living as well as medication and surgery. We can prevent diseases and injuries and live longer, healthier lives by making good lifestyle choices, and our medical professionals can help make that happen." Increasing the Safety of Prescription Drug Use Act of 2013 (S. 1657), introduced Nov. 6, 2013 Sen. Tom Udall (D-NM) introduced the Act November 6, 2013. According to Udall, it would expand medical education training and use of timely data to ensure that patients receive prescriptions safely and legally. The bill would strengthen monitoring techniques for existing high-risk prescriptions - such as by expanding the reach of a prescription drug database across states - and implement new measures to prevent prescription drugs from falling into the wrong hands. Increased patient assessment would help refer potentially addicted patients to treatment. Regarding continuing medical education, the Act states in Section 5: "The Secretary of Health and Human Services…shall award grants to States to develop continuing education criteria and review processes that allow State health profession boards or State agencies to certify appropriate education and training for informed and safe prescribing of opioids and other drugs on schedule II and III under section 202 of the Controlled Substances Act ( 21 U.S.C. 812 )." Department of Veterans Affairs Continuing Medical Education Program (S. 1863), introduced Dec. 19, 2013 The bill directs the Secretary of Veterans Affairs to establish a continuing medical education program for medical professionals with the goal of: (1) increasing knowledge and recognition of medical conditions common to veterans and family members of veterans, and (2) improving outreach to veterans and family members. Sen. Sherrod Brown (D-OH) introduced the bill in the Senate on December 19, 2013, which requires the program to include education on four issues. Education must include: (1) dealing with patients who are veterans or family members; (2) identifying and treating common mental and physical conditions of veterans and family members; (3) programs and benefits available to veterans and family members through the Department of Veterans Affairs (VA), the Department of Labor, and such other federal agencies and non-federal organizations as the Secretary considers appropriate; and (4) the VA health care system. The bill states that the Secretary of Veterans Affairs will carry out the program on the Department of Veterans Affairs website. Under the bill, The Secretary will also determine the curriculum of the program and the number of hours of credit to provide to participating medical professionals for continuing medical education. The bill states that the "Secretary shall carry out the program at no cost to participating medical professionals." Posted by Thomas Sullivan on May 13, 2014 at 05:13 AM in CME, Congress | Permalink
Senator Chuck Grassley (R-Iowa) plans to create a "Senate Whistleblower Protection Caucus." Grassley's plan coincides with the 25th anniversary of the Whistleblower Protection Act, which he co-authored. Over the next six months, Grassley will discuss the caucus with colleagues and encourage them to join with an eye on an official start in the new Congress, according to an announcement by the Congressman's office. "Whistleblower protections are only worth anything if they're enforced," Grassley stated. "Just because we've passed good laws does not mean we can stop paying attention to the issue. There must be vigilant oversight by Congress. The best protection for a whistleblower is a culture of understanding and respecting the right to blow the whistle." He added that he hopes "this whistleblower caucus will send the message that Congress expects that kind of culture." "Whistleblowers are often treated like skunks at a picnic. It takes guts to put your career on the line to expose waste and fraud, and whistleblowers need senators who will listen and advocate for them." Policy and Medicine has recently covered Senator Grassley's activities regarding the Physician Payments Sunshine Act, which he co-authored. But Grassley has been a long-time whistleblower advocate. In addition to co-authoring the 1989 whistleblower law, Grassley authored the 2006 overhaul of the IRS whistleblower program to fight major tax fraud. The Congressman's office notes that the IRS has recently paid out several awards, but has acknowledged, after scrutiny from Grassley, that the agency must be more timely and responsive in processing whistleblower claims. Grassley also authored the 1986 update of the False Claims Act to include qui tam provisions so that insiders could bring wrongdoing forward and sue in the name of the government. Over the last several years, we have covered a broad array of settlements, legal cases, and government investigations and enforcement actions regarding healthcare entities and the life sciences industry. One critical aspect of this increased enforcement has been the use of qui tam relators. In almost every major settlement, a former employee of the hospital, drug company, or medical device manufacturer used their inside information or knowledge of misconduct to bring a case against the company under the False Claims Act and took advantage of the opportunities offered under the whistleblower provisions. Click here for our article on how Sunshine Act data will help qui tam whistleblowers and their attorneys. Posted by Thomas Sullivan on April 18, 2014 at 05:20 AM in Congress | Permalink
In early March, we wrote that a bipartisan group of congressional lawmakers announced they had reached a deal on legislation to repeal Medicare's widely criticized sustainable growth rate (SGR) formula, replacing volume-based payments with measures that reward care efficiency and quality. However, it was noted that the legislation faced steep political challenges in Congress. Updating this story, it has been reported that the House of Representatives has reached a deal to delay physician Medicare reimbursement cuts under the sustainable growth rate (SGR) formula for another year. According to the 121-page bill, the House will pass a year-long extension, through the end of March 2015. The bill also extends several related healthcare measures until the end of March 2015. The year-long patch is not paid for over the long term. Instead, the bill shifts around Medicare sequester cuts due to take place in 2024, so that all of them happen in fiscal year 2024, instead of having them split between fiscal years 2024 and 2025. But that language only helps pay for the doc fix over a 10-year window, and creates no actual budget savings over a longer term. As a result, the bill also includes language exempting it from "PAYGO" rules that require new spending to be offset with new revenues or cuts. "This is a one-year patch for the SGR, something that was worked out between Speaker (John) Boehner and Sen. Majority Leader (Harry) Reid," said Stanley Nachimson, principal of Nachimson Advisors, a healthcare information technology consultancy specializing in ICD coding. "We should know by this weekend if it happens."Both leaders have pledged to allow an up or down vote, Nachimson said, with the House going first on Thursday and the Senate Friday. "This thing, I think, came up rather quickly. It caught a few people by surprise, including me." Ultimately, the last-minute agreement will likely disappoint physicians, most of whom support a previous bipartisan deal to permanently repeal the much hated payment formula. But that deal hit a snag this month when lawmakers inserted measures in the bill tying it to a delay in the Affordable Care Act's mandate requiring all individuals to obtain health insurance. The cost to permanently repeal the SGR with the ACA delay will total more than $180 billion, according to a report from the Congressional Budget Office. Additionally, the bill also contains language that would delay ICD-10 implementation until 2015, according to a statement from the American Health Information Management Association. Specifically, Section 212 of the proposed bill states that "The Secretary of Health and Human Services may not, prior to October 1, 2015, adopt ICD–10 code sets as the standard for code sets under section 1173(c) of the Social Security Act (42 U.S.C. 1320d–2(c)) and section 162.1002 of title 45, Code of Federal Regulations." In response to this legislation, Ardis Dee Hoven, M.D., President of the American Medical Association, issued the following statement opposing the bill: "Facing another self-imposed deadline, the House of Representatives is scheduled to vote Thursday on the "Protecting Access to Medicare Act," which would enact the 17th temporary "patch" to avert a 24 percent payment cut. Today, the American Medical Association and other physician groups are calling on House members to vote no on this legislation. Full repeal of the sustainable growth rate formula is the answer to strengthening the Medicare program, not another patch. "The case for repeal of the so-called SGR is stronger than ever. The bipartisan, bicameral agreement by the three congressional committees of jurisdiction for the Medicare program would improve quality, increase care coordination and lower total costs and is strongly supported by the AMA and over 600 other physician organizations. Unfortunately, differences on budgetary issues have thus far stymied final passage. By extending the Medicare provider sequester and "cherry picking" a number of cost savings provisions included in the bipartisan, bicameral framework, the "Protecting Access to Medicare Act" actually undermines future passage of the permanent repeal framework. Further, it would perpetuate the program instability that now impedes the development and adoption of health care delivery and payment innovation that can improve health care and strengthen the Medicare program. We urge the House and the Senate to continue to pursue bipartisan negotiations on permanent SGR repeal legislation and for both chambers to oppose The Protecting Access to Medicare Act." Additionally, Senate Finance Committee Chairman Ron Wyden, D-Ore., issued the following statement: "We have a choice. We can either continue on with the status quo in Medicare by enacting a 17th patch – reinforcing a flawed payment formula that jeopardizes seniors' access to their doctors, pits provider groups against each other, and fails to actually improve the Medicare program. Or, we can end the budget fiction that is the SGR, provide certainty to seniors and their doctors, and get the ball moving on bipartisan Medicare reforms – paying for value, managing chronic illness, increasing data transparency, and finally moving away from fee-for-service payment that got us into this mess. My choice is to end the status quo in Medicare by permanently repealing and replacing the SGR. There is no reason to wait." We will report more information as it becomes available.
March 27, 2014, 12:33pm: The House passed a one-year “doc fix” patch by voice vote, approximately two hours after the vote was temporarily pulled from the floor. The bill would avoid a cut in Medicare reimbursement rates until March 2015. Bipartisan legislators in the House were uncertain that the bill would get the two-thirds majority required to pass under a suspension of the rules, but the measure was quickly moved through the floor on a voice vote despite concerns that a recorded vote may not have yielded a favorable result. Passage of the bill comes on the heels of opposition from Senate Finance Chairman Ron Wyden (D-OR) and a myriad of physician groups, who have pushed for a more permanent fix to Medicare’s sustainable growth rate (SGR).
Posted by Thomas Sullivan on March 27, 2014 at 09:16 AM in AMA, Congress, ICD-10, SGR | Permalink
FDA Commissioner Addresses FDASIA, DQSA, and Opioid Abuse
FDA Commissioner Margaret Hamburg testified at the Senate Health, Education, Labor and Pensions (HELP) Committee, addressing timeliness of drug and device review, drug shortages and the supply chain, compounding implementation, and opioid abuse. Hamburg spoke to the accomplishments of the FDA Safety and Innovation Act (FDASIA) and Drug Quality and Security Act (DQSA). Food and Drug Administration Safety and Innovation Act User Fee Program Implementation FDASIA includes the reauthorization of the Prescription Drug User Fee Act (PDUFA V) and the Medical Device User Fee Act (MDUFA III). PDUFA was passed in 1992 in order to speed up the FDA's drug approval process. Both User Fee Acts allow the FDA to collect substantial fees from pharmaceutical manufacturers to fund the regulatory review of new medicines. According to Hamburg, PDUFA V addressed many top priorities by industry and the FDA. These enhancements were "funded by a modest 6 percent increase in PDUFA user fees." Under MDUFA III, FDA is authorized to collect user fees that will total approximately $595 million over five years. "In exchange for the additional user fees, FDA committed to meet much-enhanced performance goals for the device review process," Hamburg noted. "Coming at a time of continuing budget restraints, this steady source of funding is essential to support and maintain FDA's staff of experts who review the thousands of product submissions we receive every year, and do so in a timely and thoughtful manner," Hamburg states. "Over the years, our user fee programs have ensured predictable, consistent, and streamlined premarket programs for industry and have helped speed patient access to safe and effective new products." Generic Drug User Fee Amendments of 2012 The Generic Drug User Fee Amendments of 2012 (GDUFA), created to build on the success of PDUFA, is designed to speed access to safe and effective generic drugs to the public and reduce costs to industry. The law requires industry to pay user fees to supplement the costs of reviewing generic drug applications and inspecting facilities. To date, the backlog of pre-GDUFA applications has been reduced by approximately 40 percent. FDA also "facilitated development of the most comprehensive list of generic drug industry participants," Biosimilars User Fee Act The Biologics Price Competition and Innovation Act, enacted as part of the Affordable Care Act, established a new abbreviated approval pathway for biological products shown to be "biosimilar to" or "interchangeable with" an FDA-licensed biological product. Approved biosimilars are expected to be less expensive than the reference products, providing clinicians and their patients access to more affordable treatments that are biosimilar or interchangeable. Hamburg noted that because "there are currently no FDA-approved biosimilar biological products…the BsUFA program includes fees for products that are in the development phase to generate fee revenue in the near-term and to enable sponsors to have meetings with FDA early in the development of biosimilar biological product candidates." In March 2013, FDA published draft guidance for industry entitled "Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants." The FDASIA also includes (1) a provision to encourage the development of antibacterial drugs; (2) a "powerful tool to facilitate the development and review of 'breakthrough therapies,'" requiring FDA to expedite the review of a drug if "it may offer substantial improvement…for patients with serious or life-threatening diseases;" (3) provisions intended to improve the safety and effectiveness of pediatric drugs and devices; and (4) provisions to encourage development of treatment for rare diseases. According to Wolters Kluwer, approximately $56 million in 2013 user fee funds are now unavailable to the FDA due to the sequestration. . For example, the small 6 percent increase in PDUFA user fees was essentially canceled out by the amount sequestered.
Patient Engagement In addition to the reimplementation of user fees, the FDASIA also includes provisions intended to enhance patient engagement with FDA through the Patient-Focused Drug Development Program. FDA developed the program to obtain the patient perspective on certain disease areas during the five year period of PDUFA V. The FDA held a two-day public workshop in September 2013 to engage and solicit information on patient preference from stakeholders, including patients, health care providers, industry, and academic leaders, and also "recently completed an obesity pilot study that has developed new tools that can be used to measure patient preferences." Drug Shortages and the Supply Chain "Preventing drug shortages has been, and continues to be, a top priority for FDA," Hamburg notes, and FDA has "increased substantially the resources [they] devote to drug shortages and expanded [their] work to prevent them." The address noted that FDA helped prevent 170 shortages in 2013, 282 shortages in 2012, and 195 shortages in 2011. "[T]he number of new drug shortages declined significantly in 2012 to 117 and fell even further to 44 in 2013. Title VII of FDASIA strengthens drug safety in an "increasingly global drug supply chain in which nearly 40 percent of finished drugs and 80 percent of APIs are imported." Title VII allows FDA to protect the global drug supply chain by: (1) increasing FDA's ability to collect and analyze data to enable risk-informed decision-making, (2) advancing risk-based approaches to facility inspection, (3) partnering with foreign regulatory authorities, and (4) driving safety and quality throughout the supply chain through strengthened enforcement tools. Unique Device Identifier System Hamburg also discussed the FDA's Unique Device Identifier (UDI) System, aimed at providing a "consistent, standardized" way to identify medical devices. The FDA hopes the system "will provide improved visibility as devices move through the distribution chain, enhancing the ability to quickly and efficiently identify marketed devices when recalled and improve the accuracy and specificity of adverse event reports; it will also offer a clear way of documenting device use in electronic health records and clinical information systems." Drug Quality and Security Act The Drug Quality and Security Act (DQSA) was passed on November 27, 2013, and seeks to oversee the compounding of drugs and make them safer, and outlines steps to identify and trace certain prescription drugs as they are distributed in the United States. At the Senate health committee hearing, U.S. Senator Lamar Alexander (R-Tenn) stated with approval: "It has been a little over 100 days since the president signed the Drug Quality and Security Act, and in that time 30 facilities have registered as outsourcing facilities nationwide—they've done that voluntarily--and these 30 facilities all have done this without receiving guidance on the requirements they'll have to meet for the sterile drugs they make. So that's a good sign, and I believe that once we have more clarity, the number of outsourcing facilities will go up significantly." In terms of security, Hamburg outlined steps to build an electronic, interoperable system to identify and trace prescription drugs as they are distributed in the US. The development of the system will be phased over ten years with additional requirements that include: placing unique product identifiers on individual drug packages and providing product and transaction information at each sale with lot level information, in paper or electronic format. Ten years after enactment, the system will facilitate the exchange of information at the individual package level about where a drug has been in the supply chain. The new system will: Enable verification of the legitimacy of the drug product identifier down to the package level; Enhance detection and notification of illegitimate product in the drug supply chain; and Facilitate more efficient recalls of drug products. This system will enhance FDA's ability to help protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful. Opioids During the Senate meeting, Hamburg said opioid abuse is a "serious public health threat," although it is important that patients with legitimate needs be able to access needed treatments and that "hydrocodone is an important [drug] for treating legitimate pain," she said. She noted a "serious addiction threat" and said "prescriber practice is a serious component." Chairman Tom Harkin (D-IA) pressed Hamburg about the FDA's approval of Zohydro, a single-entity hydrocodone product, pointing to an advisory panel's recommendation against approval. Dr. Hamburg said the only available product also contained acetaminophen and cited concerns on liver toxicity, adding that Zohydro was "unique as a single hydrocodone product without that risk." However, according to many opponents, this makes the drug easier to abuse. Some have called for a non-crushable, abuse resistant opioid formulation (Washington Post). Hamburg stated the agency "recognizes [Zohydro] is a powerful drug" and that it "serves an important niche for pain therapy," while FDA also "understands the broader context of opioid misuse and weighs carefully risks and benefits." Posted by Thomas Sullivan on March 17, 2014 at 05:12 AM in Congress, FDA | Permalink
Last week we wrote about the unpopular proposed changes to Medicare Part D. Among the most problematic proposals was one to eliminate protected class status for several categories of medication under Part D. On Monday, in a letter to Congressman and Senators, the Centers for Medicare and Medicaid Services (CMS) announced that it had decided not to follow through on the proposed rule "at this time." Healthcare stakeholders, including the Partnership for Part D Access, applauded CMS' decision, but note that continued involvement is important for enrollees' access to important prescription drugs. Part D, also known as the Medicare prescription drug benefit, was enacted as part of the Medicare Modernization Act of 2003 and provides extensive drug coverage for seniors and the disabled, allowing them to get prescriptions as quickly as possible. Medicare Part D currently covers medicines for about 39 million beneficiaries. (Wall Street Journal). Medicare covers a long list of medications, but six drug classes have a "protected status," including antidepressants, cancer drugs, and anti-seizure drugs. Medicare drug plans are required to pay for all "protected" medicines. CMS' proposed rule had proposed to end the protected status for antidepressants and immunosuppressant drugs or transplant drugs starting in 2015 and antipsychotic drugs potentially in 2016. Last week we wrote that "the opposition to portions of the rule, or to the rule as a whole, appears to strongly outweigh any support." In a February 5 letter to CMS, every member of the Senate Finance Committee expressed opposition to the proposed CMS changes to the protected classes policy. On March 3, a bipartisan group of 50 members of the House Energy & Commerce and Ways & Means committees sent a similar letter requesting that CMS reject the Administration's suggested changes to the Part D program concerning the six protected classes policy and withdraw the proposal. Reuters mentioned that more than 370 organizations in total—representing insurers, drug makers, pharmacies, health providers, and patients—urged CMS to reconsider. CMS took note of the response. "Given the complexities of these issues and stakeholder input, we do not plan to finalize these proposals at this time," CMS Administrator Marilyn Tavenner advised in a letter sent Monday to members of the Senate and House of Representatives. "We will engage in further stakeholder input before advancing some or all of the changes in these areas in future years." The House is scheduled to vote on a bill March 11 by Rep. Renee Ellmers (R., N.C.) that directs Medicare to stop work on the proposed rule. (Reuters). Also scrapped from the initial-700 page proposal was a plan to address "preferred pharmacy networks" and a limited two drug-plan options for seniors. While CMS took heed of the enormous response to the proposed change to Part D, Marilyn Tavenner left open the door for Medicare changes in the future. We will keep you up to date on proposed rulemaking. Posted by Thomas Sullivan on March 10, 2014 at 09:51 PM in CMS, Congress | Permalink