A Detroit-area man was indicted today for obstruction of justice in connection with his alleged attempts to conceal evidence relevant to his upcoming trial for an alleged health care fraud scheme with estimated losses exceeding $30 million.

The owner of a Florida mortgage company, seven employees of the company and two real estate developers were indicted in the Southern District of Florida in connection with an alleged $50 million mortgage fraud scheme.

The Justice Department announced today the filing of a lawsuit with the Executive Office for Immigration Review against Louisiana Crane Company LLC (Louisiana Crane), which is headquartered in Eunice, Louisiana.

The Justice Department announced today that it reached an agreement with Culinaire International, a catering and restaurant management company headquartered in Houston, Texas, resolving a claim that Culinaire engaged in citizenship discrimination during the employment eligibility reverification process in violation of the Immigration and Nationality Act (INA).

A Canton, Massachusetts, man was arrested today at Boston's Logan International Airport in connection with the ongoing criminal investigation of New England Compounding Center by the Justice Department’s Civil Division and U.S. Attorney’s Office for the District of Massachusetts.

Life Care Services LLC, a manager of skilled nursing facilities based in Des Moines, Iowa, and CoreCare V LLP, doing business as ParkVista, a skilled nursing facility in Fullerton, California, have agreed to pay a total of $3.75 million to the government for causing the submission of false claims to Medicare for unreasonable or unnecessary rehabilitation therapy purportedly provided by RehabCare Group East Inc., a subsidiary of Kindred Healthcare Inc.

The owner and operator of a Miami home health care company was sentenced to 75 months in prison today for her participation in a $6.5 million Medicare fraud scheme involving the now defunct home health care company, Nestor’s Health Services Inc.

The United States has filed two complaints under the False Claims Act against Michigan neurosurgeon Dr. Aria Sabit, spinal implant company Reliance Medical Systems, two Reliance distributorships—Apex Medical Technologies and Kronos Spinal Technologies—and the companies’ owners, Brett Berry, John Hoffman and Adam Pike.

An East Side Bloods (ESB) gang member from Scottsdale, Arizona, was sentenced late yesterday to serve 30 years in prison for his role in the violent street gang, which operated on the Salt River Pima-Maricopa Indian Community reservation.

William P. Danielczyk, theformer head of a Virginia-based defense contracting company, was sentenced today to serve 18 months in prison for failing to collect and pay more than $2.2 million in employee payroll taxes and engaging in theft of more than $186,000 from an employee pension plan.

The Department of Justice announced today that it filed a motion to show cause why Bayer Corporation should not be held in civil contempt for violating a court order in the U.S. District Court for the District of New Jersey.

The Department of Justice and the Corporation for National and Community Service (CNCS), which administers AmeriCorps national service programs, has awarded $1.8 million in grants to increase the effective and efficient adjudication of immigration proceedings involving certain children who have crossed the U.S. border without a parent or legal guardian.

The Justice Department announced Monday that Attorney General Eric Holder has recorded a video message as part of the Cartoon Network’s “I Speak Up” campaign to combat bullying. The project urges young people to speak up in order to help bring bullying situations to an end.

The general manager of a Southern California ambulance company pleaded guilty yesterday in Los Angeles to conspiracy to commit Medicare fraud, conspiracy to obstruct a Medicare audit, and making materially false statements to law enforcement officers.

Attorney General Eric Holder, Assistant Attorney General for National Security John Carlin and U.S. Attorney William J. Hochul Jr. for the Western District of New York announced today that a federal grand jury in Rochester has returned a seven-count indictment charging Mufid A. Elfgeeh, 30, of Rochester, with three counts of attempting to provide material support and resources to the Islamic State of Iraq and the Levant (ISIL), aka the Islamic State of Iraq and Syria (ISIS), a designated foreign terrorist organization. In addition, Elfgeeh is also charged with one count of attempted murder of current and former members of the United States military, one count of possessing firearms equipped with silencers in furtherance of a crime of violence, and two counts of receipt and possession of unregistered firearm silencers.

Attorney General Eric Holder is set to announce a partnership between the Department of Justice’s Office of Juvenile Justice and Delinquency Prevention (OJJDP) and the Department of Housing and Urban Development (HUD). HUD will offer new grants to support collaborations between HUD-funded organizations, and civil legal aid programs and public defender offices. The grant funded collaborations will focus on expunging and sealing juvenile records – improving the chances that reentering youth will be able to obtain degrees, find work and secure housing. The announcement is set to be made this evening during the Attorney General’s remarks to the Legal Services Corporation 40th anniversary celebration.

A Plus Home Health Care Inc. and its owners, Tracy Nemerofsky and her father, Stephen Nemerofsky, have agreed to pay $1.65 million to the United States to settle allegations that A Plus paid spouses of referring physicians for sham marketing positions in order to induce patient referrals.

Benjamin Pierce Bishop, 60, a former Honolulu, Hawaii, civilian defense contractor and retired lieutenant colonel in the U.S. Army, was sentenced today by U.S. District Judge Leslie E. Kobayashi to serve 87 months imprisonment and three years’ supervised release for willfully communicating classified national defense information to a person not authorized to receive it and unlawfully retaining classified national defense information at his home.

Attorney General Eric Holder announced today that the Department of Justice and 19 states and the District of Columbia have entered into a $1.375 billion settlement agreement with the rating agency Standard &s Financial Services LLC, along with its parent corporation McGraw Hill Financial Inc., to resolve allegations that S&s 2013 lawsuit against S& true credit risks. Other allegations assert that S&s business relationships with the investment banks that issued the securities.

Misled More Than 50 Individual Investors Who Bought Bonds

A former Queenstown, Maryland, resident pleaded guilty today to securities fraud and filing a false tax return

A federal jury in Las Vegas convicted two men of conspiracy, wire fraud and securities fraud yesterday for their roles in an approximately $10 million international investment fraud scheme involving numerous victims

The former president and majority stockholder of a construction company was sentenced to five years in prison today following her plea of guilty to filing a false tax return and her conviction by a jury of conspiracy to defraud the United States, wire fraud, mail fraud, false statements, interstate transportation of property taken by fraud, conspiracy to obstruct justice and obstruction of justice, announced Acting Assistant Attorney General Caroline D. Ciraolo of the Justice Department’s Tax Division and U.S. Attorney Wendy J. Olson for the District of Idaho.

NORFOLK, Va

Two former Deutsche Bank AG (Deutsche Bank) traders—the bank’s supervisor of the Pool Trading Desk in New York and a derivatives trader in London—were indicted for their alleged roles in a scheme to manipulate the U

NEWPORT NEWS, Va

Biopharmaceutical company RedHill Biopharma Ltd. (RDHL) on Monday provided an additional update on the compassionate use program with its investigational drug, opaganib (Yeliva, ABC294640)1, in patients with confirmed SARS-CoV-2 infection (the cause of COVID-19) in Israel.

The federal government in March released a pair of long-awaited rules that will give patients greater access to their health data and improve the flow of information across care settings.

Care coordination is considered a hallmark of patient-centered treatment and has been shown to improve health outcomes and patient satisfaction as well as reduce costs. Defined as organizing patient care activities and sharing information among all participants concerned with an individual’s treatment plan in order to achieve safer and more effective results, care coordination is increasingly...

The spread of COVID-19 is placing unprecedented strain on Philadelphia’s hospitals, public health systems, and residents. Although the full effects of the emergency have yet to be realized, newly released data from 2018 and 2019 provides insight on the state of public health in the city before the pandemic.

M&A is an omnipresent reality in the biopharma industry, from Big Pharma mega-mergers to smaller acquisitions of emerging startups. We’ve recently witnessed several large M&A transactions get closed or announced, including BMS-Celgene, Takeda-Shire, and AbbVie-Allergan; according to BMO Capital Markets

The post BioPharma M&A Drives More Efficient Resource Allocation appeared first on LifeSciVC.

This blog post was written by Deanna Petersen, CBO of AVROBIO, as part of the From The Trenches feature of LifeSciVC. When AVROBIO went public in June 2018, I found myself on the steep end of an unexpected but interesting

The post Recipe For Managing Data Disclosure Successfully With Academic Partners: A Public Gene Therapy Company Perspective appeared first on LifeSciVC.

The American Herbal Products Association submitted nearly 100 pages of comments to the Food and Drug Administration Center for Food Safety and Applied Nutrition identifying ways to improve regulations, guidance documents and enforcement practices to better protect public health.

Probi's largest clinical trial ever, focused on probiotic immune health, has recently been completed.

Nutrition 21, LLC has announced its Nitrosigine® is now featured in EVERTRAIN PRE, a recently launched pre-workout supplement designed to provide athletes with sustained energy, superior focus and increased endurance.

A study demonstrated Wellmune® may protect intestinal barrier function in adults when faced with stress.

Another leading athlete has joined Arla Foods Ingredients’ growing number of brand ambassadors for Lacprodan® HYDRO.365.

InstantGMP, Inc. released a much-anticipated enhancement to the Equipment Logs feature.

Emport LLC is pleased to introduce new training programs and materials to augment its food safety and allergen control portfolio.

ChromaDex Corp. announced NIAGEN® nicotinamide riboside prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer’s disease.

Natural product brands can boost trade show ROI by investing in PR to work with trade press via press releases and onsite interviews.

The chief executive of a supplement company under investigation by FDA could go to prison for allegedly violating the terms of his supervised release following a criminal conviction in 2014.

An advertising agency agreed to settle a complaint brought by state and federal regulators over the creation and dissemination of allegedly deceptive radio advertisements for weight-loss products.

It is "inconceivable" that immunity will not remain high on the list of health priorities when this pandemic ends and now is the time to create more "convincing experiences" to ensure trial turns into adoption, according to food and drink research and branding experts.

The impact of corruption is far-reaching and devastating, especially for women.

From : Communities>>Regulatory Open Forum
Hello Jose, To my knowledge, the change of O/O does not trigger a notification that needs to be confirmed, nor does it trigger a review of enforcement history.  The change of ownership and O/O is merely an administrative update that gives FDA both current information and a history of changes.  Of course, if there are known red flags with any of the involved organizations, changes can be scrutinized. Regards, James ------------------------------ James Bonds J.D. Director Regulatory Affairs Atlanta [More]

From : Communities>>Regulatory Open Forum
This message was posted by a user wishing to remain anonymous For device-lead drug combination products, is there any difference in the quality (grade) of API used compared to a pure drug product? The cGMP guidance for combination products does not seem to specify, and since drug claims cannot be made on device-lead drug combination products, it was not clear what quality of drug is required. Thank you!

From : Communities>>Regulatory Open Forum
​I doubt FDA would have any willingness to change the requirements or expectations for a drug product based on whether it is in a strictly drug product versus in a combination product.  The fact also that there is not a published allowance for this is further evidence that FDA expects that the drug will meet the requirements as expected for drug products without providing any allowed changes or classes of changes.  Remember, FDA expects that drug products meet specific requirements.  Things like [More]

Is data integrity music to your ears?  Ours, too!

ALCOA, GAMP, Part 11, GIGO, we cover it all.
(Sung to the tune of Simon and Garfunkel's "The Sound of Silence.")

Developing safe and effective drugs requires a coordinated effort across a diverse set of disciplines. This is easier to observe at some points in the process than at others. Once a product is well into human trials, it can be easy to forget that developments on the manufacturing side of the house can affect the clinicians who are conducting the studies.




Trialed Drug vs Marketed Drug


Once researchers are satisfied that animal studies show that an Active Pharmaceutical Ingredient (API) is effective and nontoxic at initial doses, there’s an urgency to get it into the clinic and begin human studies as soon as possible. Though the ultimate product may be marketed in one form, a different form may take less time to manufacture, and so would be the form given to human volunteers in earlier clinical trials.

A tablet, for example, is much harder to manufacture than a 2-piece hard shell capsule because determining the appropriate compression for a tablet takes time. (Tablets that aren’t sufficiently compressed will break apart in the bottle; tablets compressed too tightly may not dissolve as they should, earning themselves the entertainingly accurate moniker “bedpan bullets.”) Rather than wait until a tablet form of the drug can be fully developed, to save time, sponsors would likely begin human studies using a hard shell capsule version.*

To ensure that clinical trial data for the Investigational Product (IP) are applicable to the ultimately marketed product, clinicians run bioequivalence for dosage form studies. These small pharmacokinetics studies may result in changes, such as dosage amount or frequency, if people do not metabolize the studied formulation and the final formulation the same way.


Stability Test Failures

When we hear of a pharmaceutical company having to “pull its product,” we typically think of a recall scenario that involves consumers, distributers, and retailers.  Recall procedures fall under the GMP umbrella, and are spelled out in great detail in 21 CFR Part 211. However, similar procedures may very well be required of clinical site staff, long before the product ever sees its first drugstore.


Before any clinical trials begin on a drug, manufacturers would have been conducting stability tests for months. But stability testing may continue for years after the start of human trials, and analysts could detect a variety of troubling conditions in the course of their work. Product can change color or break apart. Capsules can crack and leak. Microbes could begin to grow, especially in moister product. The container closure system itself could be problematic; it could leech contaminating material into the product, introducing impurities, or it could extract material from the product, diminishing its potency. Any of these finding could mean that study drug would need to be pulled from clinical sites.

No one expects site staff to have detailed quarantining and recall procedures; the Sponsor will tell site staff exactly what they need to do. But what would this look like?

(1) Adulterated product that cannot be dispensed will need to be moved to a separate, secure area so it won’t be confused with good product. It might need to be stored there for a period of time or shipped back to the Sponsor.

(2) For certain, a site’s drug accountability procedures will be center stage. The only way a site can successfully recall bad product is if it has -- all along -- closely tracked the amount of IP it has received, dispensed, and still has on hand.

(3) Study participants who have any quantity of the bad product will need to be contacted, told not to use it, and told how to return it. (Note that this pertains to participants on the placebo arm as well, otherwise the blind will be broken.) Phone calls may not be sufficient; sites may need to invoke lost-to-follow-up procedures, such as sending registered letters. Remote, virtual trials, which often ship IP to participants, need to be designed to allow for the tracking and retrieval of bad product.

(4) What should be done if it turns out some participants have already used the bad product? Unfortunately, that’s one SOP you can’t write in advance; it would completely depend on the nature of the IP and the problem it has, the vulnerability of the patient population, the protocol, the participant’s proximity to the site, etc. Perhaps a careful case review to look for AEs associated with affected participants would suffice. More critical situations may require participants to undergo physical examinations or special testing. In many cases, study data associated with the use of the tainted IP would need to be identified and removed from the efficacy analysis.

(5) These quarantining and recall activities must be carefully recorded. IRBs and regulators will want written proof that all suspect IP has been accounted for. Sponsors might consider sending a CRA to ensure adequate documentation.


Re-labeling

Stability tests don’t have to fail to trigger action for clinical staff. Should a chemist discover a condition that requires a labeling modification -- a new expiry date**, for example – all the labels on existing product held at clinical study sites would need to be replaced. In these situations, the Sponsor may dispatch CRAs to replace the labels themselves, or negotiate with individual site staffs to do it instead. 


No GxP is an Island…

GMP professionals manufacture, package, and label biopharmaceutical products. GCP professionals conduct clinical trials on those same products. These roles are very different from each other, yet they don’t work in isolation. Formulation changes, stability testing, and re-labeling requirements represent three examples in which activities performed by GMP folks impact their GCP counterparts. Have you experienced any additional examples? Feel free to share them in the Comments section.

In case you missed it, our last post was about how attributes of the Study Drug influence the Site Selection and Feasibility process.

___________________________________________________________

* “By the time clinical trials start, they know what ingredients go in the cookie, they just don’t know how the cookie is going to turn out yet.”
       - Rosanne Sylvia-Heeter, Polaris Director of GMP Compliance and phenomenal cook

** Expiry dates are not required but are sometimes included on IP labels.

Guest Blogger: Greg Weilersbacher
Founder & President, Eastlake Quality Consulting

All companies outsource. It’s a humbling fact that you simply can’t do it all yourself. This often has to do with resource allocation; your company may allocate dollars to build and sustain some activities in-house while choosing to contract higher-cost operations to qualified suppliers who already have the expertise and equipment. 

You may outsource the manufacturing of tablets, sterile injectable, or topical dosage form, or the GMP release and stability testing of your product. Once the production and testing is complete, the product may need to be stored under controlled temperature and humidity conditions and then distributed to locations around the globe. The Contract Development and Management Organizations (CDMOs) who execute these critical operations are of paramount importance to your company’s success. Choosing the right suppliers will also help to minimize stress-induced headaches throughout your organization. Here are the top five ways to get the most out of a supplier audit.



1.  Come to the Audit Prepared
This seems obvious. However, more often than not, quality auditors step into the supplier’s lobby without doing their homework. Ask yourself the following questions: Why am I auditing this supplier? Is this supplier new to my company or one that we have used before? If used previously, have I read over the audit observations as well as the supplier’s responses and do I understand them? Which audit observations do I suspect would be the most challenging for the supplier to address and which are most important to my company’s requirements for this product? Have I reviewed previously executed production batch records and testing data and are there issues that need to be resolved? Are their deviations and CAPAs to follow up on?

Your understanding the supplier’s work proposal is of great value in refining the scope of the audit. Ask yourself:  Which of our products may be manufactured and tested here and which strengths (e.g., potency) will be produced? Which equipment is likely to be used? For a tablet production, the equipment train could include balances, blenders, roller compactor, spray dryer, solvent-rated oven, comils, tablet press and tooling, gravity feeder, coating systems, de-duster, weight sorter, metal detector, tablet counter, etc. This list of equipment will assist you in requesting equipment records during the audit. 

2.  Stay On Point
Proper audit planning will help to keep the audit organized and adhere to the audit timeline. In advance of the audit, provide the audit host with a list of the technical, lab, and manufacturing staff you wish to speak with and the records you need to review. A well-organized host will have this available for your review. Stick to your audit agenda. This is critical. The best way to derail your progress is to spend precious time chasing down minor issues while glaring problems get little to no attention. Continually refer back to the audit agenda and remember to keep the content of your audit report in mind while executing the audit.


3.  Know Your Technical Expertise and Limitations
Many auditors have led previous lives in the laboratory or in manufacturing while others started their careers in quality assurance and may have little technical background with regard to equipment, manufacturing processes, GMP utilities and laboratory testing. Know your limitations and if necessary strengthen them by hiring an expert consultant to assist you during the audit.

A common problem area that is at best glossed over and at worst completely ignored during an audit is the CDMO’s compliance with GMP utilities requirements. All too often, this is due to the auditor’s lack of understanding of the operation, inputs and outputs, validation parameters, and periodic testing and maintenance requirements for utilities such as HVAC, clean or pure steam, purified water and WFI systems, autoclaves, clean compressed air, nitrogen and other gases used for operating equipment or used during processing activities in manufacturing. Typically, these areas are also less well understood by the CDMO’s employees and as a result noncompliance abound. 

Some GMP utilities may be connected to the facility’s building management system, while others may be stand-alone equipment. In either case, the CDMO should have records of alarms (e.g., out of specification or out of range conditions), an acknowledgement of each alarm by designated staff members, and documentation of corrective actions. The last item is key. This is where the execution of quality systems tends to fail. Make a point to request documentation of corrective actions for each utility alarm. 

Additionally, purified and WFI water systems along with gases, such as clean compressed air and nitrogen, require periodical sampling/testing at each point-of-use. Verify that the timelines (monthly, quarterly, or annual) for sampling and testing were performed as directed by the CDMO’s procedures. These timelines are typically not well adhered to. A clear understanding of all the operations of the supplier’s GMP utility management process will keep your thoughts clear during the audit and help identify areas that are in need of improvement. 

4.  The Auditor’s Job is to Identify the Good and the Bad (Not to Win the Debate)
An important goal of a supplier audit is to identify the supplier’s strengths and weaknesses and come away from the audit with a compliance assessment that your company can use to make important decisions. It is of no value to your company if the goal of the auditor is to show the supplier how much he or she knows by debating the fine points of compliance. GMP auditors with decades of experience generally avoid this competitive exchange as it is unproductive. Rather, it is more important to the spend the necessary time identifying compliance issues, making them known to the audit host in a professional manner, and taking detailed notes that assist in writing the audit report. Your company’s senior managers need to know the supplier’s good and not-so-good points; detailing all of these provides the greatest value. 

5.  Interview the CDMO's Lab Staff, Manufacturing Operators, and Shipping/Receiving Personnel
CDMO’s quality systems are generally written by managers and directors who have many years of industry experience. It is of utmost importance that staff members who execute these systems understand them if your company’s product is to be manufactured, tested, stored, and distributed in a compliant manner. Request to speak with manufacturing staff members who work on the production floor and are likely to work on your product. Ask them about the process they would follow to conduct lines clearance, charge powders to a blender, operate a spray dryer, use a comil, set-up of a tablet press, inspect tablets, use metal detectors, etc. Compare the information they provide to the CDMO’s SOPs to determine if the staff understands their jobs. Listen for phrases such as “I usually do it this way…” or “it’s a different every time but I typically set up the equipment like this…” These phrases reveal a lack of control and adherence to procedures. 

The Take Away
The audit itself lays the foundation for a relationship with the supplier and the take-away message should address the following questions: Will the supplier work to resolve the issues I’ve identified? Am I confident that the supplier will immediately notify and involve my company’s representatives when deviations occur during production or testing? Do the supplier’s quality systems and records meet my company’s requirements and those of regulatory agencies? How confident am I that the supplier will produce and/or test a quality product that my company can stand behind? Is the supplier simply a pair of hands or are they committed to be my partner in this product’s success? The answers will provide you with a comfort level in making the decision to move forward with the CDMO or to look to the their competition.  

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A version of this article was first published in Outsourced Pharma.

 About the Author
Greg Weilersbacher is the Founder and President of Eastlake Quality Consulting, a GMP consulting firm based in the Southern California area. Over the last 25 years, he has held director and vice president positions leading Quality Assurance, Quality Control, Analytical Chemistry, Materials Management, GMP Facilities, and Product Manufacturing in biotech and pharmaceutical companies. His unique experiences and technical background have led to the manufacture and release of hundreds of solid oral, sterile, and biologic investigational products to clinics in the U.S. and abroad. Email Greg at weilersbacher.greg@gmail.com.