These fact sheets can be found here and are written for Manufacturers, Physicians, Teaching Hospitals and Group Purchasing Organizations (GPO’s).  These fact sheets can be utilized as an awareness tool for your employees, physician partners and distributors.

A research payment, fellowship support or space rental fees made to a facility by a manufacturer will also need to be tracked.  Utilization and integration of the PDF dataset of teaching hospitals into your physician transparency documentation processes is a necessity.  The CMS provided list identifies the recipients for whom payments will need to be tracked and the facility identification data which must be included in your submitted report.

CMS recently scheduled an Open Door forum on this topic.  Additional information and registration information can be found on the CMS website.

In reviewing the CMS OPEN PAYMENTS website it is also interesting to note that they have a specific section on audits and penalties.  It is very clear that CMS will conduct audits and any penalties “collected will be used by CMS to implement OPEN PAYMENTS”.  CMS has a clear incentive and need to impose penalties as this will fund the ongoing operations of the program.

An applicable manufacturer should ensure that they are currently collecting all the required data in an easily reportable format and can provide supporting records related to the transfers of value in the event of an audit.

To assist our clients MCRA has developed a low cost, web based, secure software solution that can not only efficiently aggregate all physician payment data but also manages the entire compliance program.

Key features include:

• Capture, Track and Report all Aggregate Spend
• Manage HCP Relationships and Contract
• Contains National Salary Data to Compute a FMV Hourly Rate
• Includes a 24 / 7 Compliance Hotline / Website
• Complete management of all elements of an effective compliance program, including tracking all policies and procedures, issues and other required elements of a compliance program.

Please contact me to schedule a brief complimentary discussion and demo surrounding this new service offering from MCRA.  I can be reached at 860-904-4451 or by email at cgingras@mcra.com.

Although the court did not clarify what promotion is allowed and what is prohibited under its decision (there was little transparency on what is still false and misleading), this ruling potentially opens the door to many marketing possibilities for the industry. As a result, this should allow the discussion of generally accepted off-label uses of devices. To be clear, this ruling certainly does not allow companies or their representatives to disseminate false or misleading information, especially when harm to patients is likely to result.

So why should the entire industry pay attention to this ruling? Does it have any practical effect on my company’s current situation? Is this a go-ahead to become more liberal when reviewing my marketing material? What are the potential consequences?

The industry wants answers to these questions and more, but reality is more qualitative than quantitative. Exact regulation and guidance for all situations that can arise in the industry is difficult for the FDA to generate.

Nevertheless, we believe that this decision should not be construed as allowing companies to create promotional materials for direct marketing of the off-label uses of their products. The ruling simply allows the open discussion of legitimate off-label uses between companies, their representatives, and physicians. This was previously only possible if the physician initially approached the company for information.

The reason for this is that by currently allowing off-label marketing on free speech grounds, the Appeals Court decision opens the door for companies to more broadly market their technologies based on un-vetted effectiveness claims, rather than stringently reviewed effectiveness evidence. On-label indications often have a body of clinical evidence in support, while off-label claims often do not have this same level of evidence review. As a result, the differentiation between what is a strong and valid claim and a misleading claim can be unclear.

There can be a number of unexpected consequences for companies which perform off-label marketing of their products, especially when they erroneously believe that these off-label uses are considered legitimate by the medical community. The FDA may still warn companies for the open marketing of off-label uses of products, and companies may still be held liable for invalid claims. In addition, it is possible for this appeals court decision to be reversed in the future.

How can you avoid off-label marketing risks in the medical device world?

Despite the seemingly looser requirements for marketing, the regulatory landscape still exists, and must be carefully followed. Though the door to off-label marketing has now been cracked open, there is still potential for it to be closed again in the future.

In order to avoid the potential costs associated with off-label promotion, medical device manufacturers should be sure to have their marketing materials reviewed by a regulatory expert to ensure that they are not promoting off-label claims. Alternatively, value may be created by dedicating resources to turn these off-label claims into on-label claims which pass regulatory muster.

In the accounting provision section of the FCPA, organizations are required to maintain strong internal controls that will provide reasonable assurances regarding the reporting of financial information.  One of the most critical internal controls that an organization MUST implement is an effective compliance program.  The presence of an effective compliance program will help prevent FCPA transgressions from occurring and will factor into the extent of the governmental punishment should an issue arise.

As indicated in the guidance, the government will ask three basic questions when evaluating the effectiveness of the organizations compliance program.  These are the exact same questions senior leadership and the Board should be asking of the Compliance Officer.

1. Is the company’s compliance program well designed?
2. Is it being applied in good faith?
3. Does it work?

Are you prepared to answer these questions with factual, independent data?

In order to adequately answer these questions an organization should conduct an independent assessment of their compliance program to ensure that it meets the standards expected by the government.   Upon completion, a report should be provided to senior leadership and the Board which will demonstrate adequate oversight of the compliance program.

A thorough assessment should start with an anonymous employee survey to gauge compliance program awareness.  These results will go a long way towards demonstrating program effectiveness and that the appropriate tone at the top has been set.  Afterwards, the assessment should thoroughly compare the existing program against governmental guidance and industry best practices.  The Office of Inspector General (OIG), U.S.  Securities and Exchange Commission (SEC), U.S. Sentencing Commission (USSC) and many other governmental entities have published a trove of helpful information.

In addition, audits of high risk areas such as anti-bribery and healthcare provider relationships should be conducted.   As an example, a Compliance Officer (or outside auditor) should conduct a comprehensive evaluation of the process to contract with healthcare professionals and contracts should be pulled to validate payments were made accurately with supporting documentation and an FMV analysis on record.

The value of a compliance program cannot be overstated and an audit provides organizational assurance that it is working effectively.

The clinical evaluation summarizes the safety, effectiveness, and risks and benefits of the device as supported by clinical data. Depending on the device classification, a clinical evaluation can include, but is not limited to, the following support data:

• literature review of published, clinical data on the subject device or similar systems*,
• internal manufacturer data,
• national and international device databases/registries data, and
• clinical investigation data.

*Evidence demonstrating system equivalence is required. Comparability data can include technology, indications and intended use, shape and dimensions, principles of operation, and materials.

Once the initial evaluation has been completed, the technical file has been reviewed by the notified body, and your device has been successfully CE Marked, the initial clinical evaluation must be actively updated at regular intervals with data obtained from Post Market Surveillance and newly published literature (as applicable).

A well-developed initial clinical evaluation can easily be updated with appropriate record-keeping of the literature search protocol including inclusion and exclusion criteria, literature search terms, a summary of the article selection process, reference listings, and organized, up-to-date documentation of post-market surveillance data (e.g., investigational plan, informed consent forms, relevant Ethics Committee(s) documentation, case report forms (CRFs), and adverse event information).

Device manufacturers benefit greatly from developing and maintaining a thorough and informative clinical evaluation document. Benefits include regulatory conformance and a better relationship with their notified body, ease of adhering to local reporting requirements, identifying new risk-benefit information that may affect device safety or labeling, and valuable insurance coverage data.

Is it time for your clinical evaluation to be updated?

In the United States, few Food and Drug Administration (FDA)–approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA.

In this journal article, we discuss the necessary steps for FDA application and approval for a new cartilage repair product, as cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market.

As discussed in the article, recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product’s attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study.

Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

The proposed rule further states, “Under the proposed system, the health care community and the public would be able to identify a device through a UDI that will appear on the label and package of a device.  The UDI will provide a key to obtain critical information from a new database, the Global Unique Device Identification Database (GUDID), which will include information important to the identification of devices.”  UDI is based on automatic identification and data capture (AIDC) technology and will follow established international technical standards.  The standards are included in the proposed new 21 CFR Part 830, Unique Device Identification.

So what is UDI?  Simply stated, on the FDA website, “A UDI is a unique numeric or alphanumeric code that includes a device identifier, which is specific to a device model, and a production identifier, which includes the current production information for that specific device, such as the lot or batch number, the serial number and/or expiration date.”

And lastly, why this posting asks are you ready?  The proposed revision of 21 CFR Part 801 – Labeling, has the following information on the effectiveness of when UDI must be on devices after the publication date of the final rule:

• Class III medical device or a device licensed under the Public Health Service Act – 1 Year
• Class II – 3 Years
• Class I and devices not classified – 5 Years

The bottom line – FDA has issued a proposed final rule and is expecting industry to be ready to comply with the regulation once it is final.

Webinar Summary: As health plans place more and more roadblocks for coverage of new technologies and procedures, the technology company’s strategy for handling denied cases becomes even more important. Most companies offer a billing guide or reimbursement toolkit to providers and other stakeholders, but often these resources lack specificity and key information that demonstrate the need for patient access to the technology or procedure.

During this webinar, Tim Hunter, Vice President of Health Economics, Reimbursement & Public Policy and Tina Murphy, Senior Manager, Patient Access Management, will provide an overview of current new technology denial trends, describe the importance of providing detailed prior authorization and claims denial resources to providers and patients, and offer recommendations to ensure that health plan decision makers are approving or denying a case based upon the correct evidence.

Please do not hesitate to get in touch with me at 202-552-5811 or by email at ebaldacchino@mcra.com if you have any questions regarding this webinar or MCRA’s reimbursement consulting services.

In the United States, human tissue products are generally exempt from pre-market review by the FDA, provided they meet certain requirements. One of these requirements is that the tissues be “minimally manipulated”. Examples of human tissue that meets the “minimally manipulated” standard include organ transplants, blood transplants, allograft bone processed to remove lipids and cells, bone demineralized via acid treatment, and production of autologous platelet rich plasma (PRP) using a centrifuge for bed-side treatment. As such, all of these treatments are exempt from FDA pre-market review, except the centrifuge that produces the PRP.

However, the process used by Regenerative Sciences is described as follows:

“This procedure, called the Regenexx^TM procedure, is used to treat certain orthopedic conditions, such as osteoarthritis, nonhealing bone fractures, avascular necrosis and bulging lumbar discs. In this procedure, the physician takes bone marrow from the patient’s hip or synovial fluid from the patient’s knee, as well as blood from the patient, and transports these materials to a nearby laboratory facility.

At this facility, mesenchymal stem cells are isolated from the bone marrow or synovial fluid and expanded in culture for two to three weeks using growth factors from the patient’s blood, as well as other chemical reagents. The cells are then combined with drug products, such as doxycycline, which have been previously approved by the FDA, and are then transported back to the clinic for injection into the patient.”

The district court sided with the FDA in deciding that process Regenerative Sciences utilized for processing the cells fell beyond the scope of “minimal manipulation”.

However, FDA’s view that these processing methods fall beyond the scope of “minimal manipulation” is not new. Genzyme’s Carticel, FDA approved under a Biologics Licensing Application (BLA) since 1997, is a procedure similar to the one outlined by Regenerative Sciences. Carticel is produced by isolating a small portion of a patient’s knee cartilage, from which the patient’s cells are isolated, expanded in cell culture, and re-injected into the patient.

In particular, the expansion of cells, which involves the addition of many reagents and growth factors in a sterile environment, is the key step that takes the production process beyond minimal manipulation. Many chemical entities are added to stimulate the cells to divide and grow to obtain enough cells for therapeutic success. These processes, as demonstrated by laboratory science, can change the nature of the cells such that they are not necessarily the same as the ones removed from the patient. While these changes could be beneficial in some circumstances (such as increased ability to repair damaged tissues in the body), there is inherent risk that the cells could cause an adverse reaction in the patient due to these changes to the cells. In FDA’s view, these treatments should be held to the same standards of safety and effectiveness as drugs and medical devices prior to use.

The WSJ article authors state:

“Federal regulators have stretched that definition to the point where a reasonable limit no longer exists. The law provided a clear impediment to unrestrained exercise of FDA authority. Something needed to be an “article”—not a medical procedure—in order to become a drug. The constraint that a drug needed to be a “thing” has been read out of the law by FDA, and the district court appears to have accepted that position.

If human cells processed by the Colorado doctors are “drugs” under federal law, even when these cells are returned to the same patient who donated them, there may be little to prevent the FDA from imposing its drug-approval requirements on any cell-based procedure.”

The authors’ inferences that the FDA is ever-stretching its boundaries of its review and that they can impose requirements on any cell-based procedure are misleading. As demonstrated by the Carticel example, this view by the FDA of cultured cells as being medical products, even if sourced from a patient’s own cells, is a 15 year old precedent. Furthermore, regulations prevent the FDA from reviewing many types of cellular procedures involving a patient’s own cells, provided they meet the “minimal manipulation” standard. Regulatory precedent has demonstrated that procedures involving separation of cells via centrifugation, simple mixing of cells (as in in vitro fertilization), and implantation without culture of these cells clearly fall within the boundaries of minimal manipulation.

In its current view, the FDA requires rigorous non-clinical and clinical data to determine the safety and effectiveness of these cellular-based treatments.  While stem cell treatments and other cell-based treatments can provide exciting advances in the practice of medicine, the safety and effectiveness of these treatments have yet to be determined and successful results from isolated case reports should be viewed with scrutiny.

An examination of the orthopedic and spine PMAs shows that approvals can typically take an average of 26 months, but range anywhere from 9 to 42 months. (However, there are outliers. In 2009, one hip device was cleared after 74 months of review.) To further break it down, spine approvals averaged 18.3 months in review, while the orthopedic approvals averaged 29.6 months in review. Additionally, the review times have been trending higher in recent years, while the number of cleared PMAs has grown smaller at the same time.

The reason for this is that the standards for clinical evidence have been growing more stringent over the past 10 years. Up to 2006, the approval process simply focused on the following questions:

• Did you “win” the study by demonstrating non-inferiority?
• Was the proper indication studied, and was the control group correctly matched to the treatment group?
• Was patient accountability high?
• Was a simple, but proper, statistical plan utilized?
• Were adverse events understood, and is a plan to mitigate them properly implemented?
• Were there quality study sites?
• Are good manufacturing processes in place?

When comparing spine and general orthopedic PMA approval timelines, it is clear that the answers to these questions play a large role in affecting outcomes. A side-by-side comparison of some areas where these PMAs differ is revealing:

[Click image to enlarge]

Newer PMA applications also are seeing a greater rigor, which has already been reflected in many of the spine PMAs approved by the FDA, thus explaining why spine PMAs have a smaller average review time. The agency now demands a greater emphasis on:

• Data analysis independence- elimination of bias
• Study safety measures- implementation of stopping rules
• Radiographic protocol- determine what is happening at the biomechanical level
• Good manufacturing processes- scrutiny of cleaning and sterilization processes
• New concerns- materials, radiographic “safety”, and mechanism of action

There are also more detailed risk-benefit determinations. Reviewers now expect peri-operative measurements, amongst other metrics, as part of the data package accompanying PMA applications. This is simply because the FDA is seeking the highest scientific rigor, in order to maximize patient safety.

How can companies optimize their navigation of the PMA process? The recipe is simple:

• Have adequate pre-clinical testing
• Demonstrate non-inferiority
• Maintain high patient accountability
• Ensure development of a positive risk/benefit profile
• Minimize “unexpected” adverse events and observations
• Clearly demonstrate the device’s mechanism of action
• Eliminate potential sources of bias during data gathering and analysis
• Maintain a validated manufacturing process

While the PMA process will be getting more and more difficult in the coming years, there are certainly ways to effectively and affordably bring medical devices through the PMA process. It takes careful planning, and knowledge of what the FDA is looking for.

Despite a long-standing evolution in patient care, and widespread use of lumbar fusion techniques for DDD diagnoses, sects in clinical and payor communities have argued that the base of scientific evidence for the continued use of this treatment option for DDD is insufficient. The Medicare program covers lumbar fusion for treatment of DDD at this time, as CMS has not issued any National Coverage Determination (NCD) which would limit coverage for such reasonable and necessary medical services. However, since 2008 a number of commercial health insurance plans have begun to limit or even deny coverage of multi-level lumbar fusion procedures for DDD indications. The origin of many of these non-coverage or ‘coverage-with-limitations’ policies may be linked back to November 30, 2006, when CMS sought recommendations on lumbar fusion for DDD from a panel of experts convened as part of its Medicare Evidence Development & Coverage Advisory Committee (MEDCAC).

In Part One of this White Paper series, MCRA provides an overview of CMS’s NCD process, and details the origin and pivotal role of the MEDCAC. MCRA also critically analyzes evidence presented and reviewed at this 2006 meeting, and introduces some of the main issues identified by committee members in reviewing the body of evidence available for lumbar fusion for DDD.

Electronic copies are available on MCRA’s homepage, while printed copies may be requested by contacting me at ebaldacchino@mcra.com or 202-552-5811. Part Two of this White Paper series, which delves deeper into precise issues identified as problematic to lumbar fusion’s evidence base and compares more recently published clinical literature in order to evaluate lumbar fusion’s continued viability, is expected to be published in late July 2012.