DarshanTalks Podcast

Although pharmaceutical drugs have been blamed for their role in the opioid crisis, they are not the only factors at play. In addition to bad players in the pharma industry, including the producer of Oxycontin, clinicians have also played a role in the ongoing crisis–over-prescribing opioids to patients who do not require it any longer. In this post, we will investigate some causes of the opioid crisis, and how the U.S. Food and Drug Administration (FDA) and other lawmakers have been responding to this crisis. 

“Feel No Pain”

One tenet behind clinicians’ approaches to treating patients is called the “Patient’s Bill of Rights,” which purports that it is unacceptable for a patient to be in any pain. Although most health care providers aim to ensure that their patients are not in pain, there comes a point when their efforts are taken too far. When attempting to treat a patient, it is possible for clinicians to over-prescribe medication because they do not have an intimate knowledge of their patient’s pain. It therefore becomes important that the patient inform the clinician about his or her pain needs and what they require for their pain. 

FDA Responses to the Crisis

To better address the opioid crisis, the FDA has been working to put into place the Risk Evaluation Mitigation Strategies (REM) system. This system is a drug safety program that would work toward mitigating some risks of opioids and controlling the effects of opioid producers. It would require that healthcare providers undergo training to be well-informed about the safety risks of the drugs they are prescribing. Besides developing this system, the FDA has also strongly suggested the removal of certain opioids from the market. The opioids that were targeted in this directive were those with a formulation that could be easily broken apart, making it easy to abuse by taking large doses together. The FDA took these steps as part of an effort to ensure that the benefits of opioids outweigh its risks.

Baseline Pain

Although it becomes easy to place blame solely on pharmaceutical drugs for the current opioid crisis, this ignores the responsibility that people have in fighting the crisis. For doctors, there is only so much that they can know about a patient’s pain–it is up to the patient to judge what the best course of action for pain treatment is. Patient accountability means that patients need to stop or reduce taking pain products when their pain dissipates to avoid potential addiction. Where a patient’s pain has gone on longer than 3-5 days, they should consult with a doctor to consider alternative medicines such as Ibuprofen, which sometimes may treat their pain better than morphine. 

American society has normalized the idea that pain is unacceptable. It is important to keep in mind that a certain amount of pain is normal. In training at a gym, for instance, there is some quantity of pain that a person has to endure while working out that is unavoidable and not necessarily harmful. When it comes to patients, debilitating pain should be avoided. However, a certain baseline of pain might not require medication–particularly not prolonged use of opioids. 

How Long is Too Long?

Depending on the pain, it is necessary for individuals to talk with their doctor about the right amount of time to stay on pain ...

Setting up effective, compliant investigational drug pharmacies means reviewing Food and Drug Administration (FDA)  requirements and applicable state boards of pharmacy.  Depending on the regulatory body reviewing the pharmacy, different parameters may need to be met. It is also important to have a well-developed process in place to ensure the accuracy and precision of drug products. 

What Do State Boards Look for?

The state board of pharmacy tends to be associated with the practice of pharmacy, which may be specific based on each state.  State boards deal with pharmacies at an individual level, and aim to ensure that facilities meet the requirements of the state board, and are appropriately registered and staffed.

What Does the FDA Look for?

In contrast to state boards, the FDA takes a more exhaustive approach.  The FDA generally looks for the compounding of marketed and unmarketed products which are able to meet the same accurate and precise measures every time.  In order to meet this standard, investigational pharmacies must focus on developing several processes.

What Should Companies Focus on?

Setting up a quality system

In order for companies to make sure that their products are consistent, an effective quality system must first be put into place.  Quality control involves testing and inspecting product components to ensure that they meet approved specifications. All of the different specifications should be met before being put into the quality system so that quality is designed and manufactured into the product itself.  This process is often referred to as “quality by design.”  

When setting up a quality system, one of the common setups that is used is the Deming or Plan-Do-Check-Act (PDCA) cycle.  This cycle allows companies to produce precise, accurate results every time.

Corrective and preventative actions

The FDA will typically look at seven major components of quality systems when measuring accuracy and precision.  They are mainly looking to make sure that there is a process in place to correct potential problems, and generate preventative actions.

A corrective action involves addressing immediate problems and taking action to ensure that they are dealt with.  However, companies need to focus on more than this and take preventative action to ensure that future problems do not arise.  In order to take preventative action, companies must often perform a root cause analysis to evaluate why and how a given problem happened in the first place.  

Production and process controls

For production and process controls, the FDA will generally review process design, process qualification and continued process verification or validation.  

Process design is involved at stage one, and refers to the commercial manufacturing process.  To meet FDA standards, companies must demonstrate that their manufacturing process is appropriately designed.  The manufacturing design is evaluated on the basis of how well it can reproduce commercially manufactured products.  Next, companies must demonstrate ongoing assurance during production to ensure that the process remains controlled.

The process of validation requires companies to detect sources of variation in their products.  Further, companies must understand how this variation might impact the process and product ...

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Bypassing FDA Approval and Bringing Your Product to Market Faster

Although it may seem that products must go through the process of obtaining the U.S. Food and Drug Administration’s (FDA)  approval to be considered safe for consumers, there are certain cases in which products can go directly to market without ever needing to be reviewed by the FDA.  The reasoning behind this is that the FDA wants to balance innovation against safety, and permit innovative products to be able to reach the market. The FDA also might allow products to skip the approval process if they are duplicates of another product that has already been approved, or if they are part of the practice already and the observable risks remain minimal.  

Dietary Supplements and Alternative Pathways

One type of product not subject to FDA approval is dietary supplements, which have been ruled by Congress as being a food rather than a drug.  As long as supplements do not make drug-like claims, such as purporting that they treat heart disease, they are not regulated like drugs and their marketing is not regulated by the FDA, but is instead regulated by the FTC.  This means that dietary supplements can reach market much faster than their drug counterparts, however, this also means a higher amount of competition because the market is oversaturated with competing supplements. Although the dietary supplement market is large and highly profitable, the amount of competing players in the marketplace makes alternative pathways to market more enticing.  

OTC Drugs

One of these other options includes the marketing and sale of OTC drugs. OTC drugs can come onto the market using the New Drug Application (NDA) pathway, or the OTC monograph pathway.   The OTC monograph pathway does not require FDA approval, and instead offers a way for drugs to reach the public much more quickly.  As long as companies meet conditions and make specific claims that match those listed on the FDA’s product list, companies are allowed to bring their product to market without FDA approval through this pathway.

Compounding Pharmacies

Yet another method of bringing products directly to market is through the use of compounding pharmacies. Compounding pharmacies do not need to notify the FDA about what specific products they are making until after the products have been brought to market.  One of the reasons why compounding pharmacies remain unregulated is because they function as a sort of “safety valve” in case of accidental shortages in certain kinds of medication, and as a consequence, the drugs produced by these pharmacies are able to reach the marketplace at a much faster rate.  Although these pharmacies are an expedient way to quickly get drugs to market, they do come with their shortcomings--including the fact that they are regulated by state boards of pharmacy, and require the oversight of a pharmacist. Recent FDA inspections have also revealed problematic findings in these types of facilities, which brings these pharmacies closer under FDA observation.  

510(k) Pathway

In the case of the 510(k) pathway, a given company must demonstrate a product’s likeness to another FDA-approved, legally marketed device (or a predicate device).  Certain products are able to bypass this pathway altogether, and put their product on the market directly. These products include devices like toothbrushes and certain cannabis-based products whi...

Recent Increase in Anti-Kickback Settlements Among Drugmakers

Already, the month of June has seen drugmakers Mallinckrodt and Insys face settlements with the Department of Justice due to allegations that they had bribed doctors and set up sham speaker programs.  These suits come after leaked information suggesting that another drug company, Novartis, may be hit with similar charges. In the case of Mallinckrodt, the company had bought another company called Questcor, and had paid doctors to increase growth for their drug Acthar while using “dirty data” to hide its illicit marketing strategies.  As for Insys, this company was sued due to its scam involving paying doctors through a fake speaker’s program between 2012 and 2015. The future of Novartis looks similarly grim, particularly now that the government is investigating its actions, and it could face close to one billion dollars in settlement.  

Are Compliance Programs Working?

One question that this string of cases has raised is whether or not the compliances programs in place at these companies have actually been effective.  The Department of Justice has released some guidance on this subject, and one of the primary actions they suggest is that companies work on the development and distribution of codes of conduct.  Further, they recommend that companies designate a compliance officer or team to report directly to a board of directors, and open up lines of communication between the two groups by using processes such as hotlines.  Other techniques such as audits and risk evaluations should also be used to help boost compliance within companies.

How Are Compliance Programs Assessed?

The U.S. Department of Justice released a new guidance document on April 30th 2019 regarding the evaluation of compliance programs—primarily dealing with these programs’ level of effectiveness.  Federal prosecutors refer to this document when determining whether or not to charge a given corporation, and so it becomes important for companies to ensure that their compliance programs are meeting this document’s guidelines.  According to the guidance, prosecutors should look at the seriousness of the offense, including the risk of harm to the public, as well as complicity in wrongdoing by corporate management and the company’s history of similar misconduct.  

How Companies are Prosecuted

These companies are prosecuted in a variety of ways depending on different factors.  In the case of Novartis, for instance, it might not make sense to exclude this company due to the significant and harmful impact that exclusion may have on the public.  Some of the other factors that prosecutors must consider before enforcing penalties include whether or not a company’s compliance program is well-designed, effectively implemented, and works in practice.  Depending on these factors, it may be appropriate to dissolve corporate criminal cases by means other than indictment, such as by deferred prosecution agreements. Overall, there is a significant amount of information and guidance surrounding how to prosecute and charge in cases of healthcare fraud.  Companies looking to market their products should remain vigilant in ensuring that their own speaker systems are compliant with federal laws, and should consider setting up compliance programs—an integral part of preventing potential scams and the resulting penalties.

The Critical Role Legal Plays on Promotional Review Teams

Legal plays a critical yet often overlooked role in promotional review teams--ensuring that companies remain compliant with federal regulations and avoid costly fines and penalties.  In the case of opiate manufacturer Insys Therapeutics, the company was recently forced to pay as much as $225 million in settlement to the government as a result of criminal and civil investigations into Insys’ marketing practices.  This case marks a rare instance of prosecutors holding executives responsible for the opioid epidemic, and also demonstrates some of the more drastic repercussions companies face as a result of bribery and illegal kickbacks.

Insys Therapeutics’ Sham Speaker Program

Insys Therapeutics was primarily targeted by the federal government for its bribery scheme in which it provided kickbacks to physicians to prescribe large amounts of its potent opioid painkiller, Subsys.   Subsys was originally intended for use by cancer patients suffering with significant amounts of pain, however, due to the company’s kickback scheme, this drug was being over-prescribed to patients who did not require such a powerful narcotic.  In an effort to induce physicians to over-prescribe its drug, Insys Therapeutics set up a sham speaker program in which it paid doctors to write prescriptions, rather than give speeches endorsing the drug. As a consequence of Insys Therapeutics’ bribery scheme, as many as five of its top executives have been found guilty of racketeering conspiracy by the federal jury, including founder John Kapoor--one of the highest ranking pharmaceutical executives to be convicted amidst the opioid epidemic.  As one Insys spokesperson commented, the company itself was in danger of folding due to the massive amounts of fines that it was facing, including a hefty fine of $225 million to end the settlement.  

Mallinckrodt’s Drug Bribery Case

Another parallel case can be seen in Mallinckrodt, which is expected to pay $15 million in an effort to settle with the U.S. Department of Justice after allegations that Questcor Pharmaceuticals, acquired by the company in 2014, had bribed doctors to prescribe its drug H.P. Acthar Gel.  The drug itself, primarily intended to treat seizures in children, had its price exponentially raised from $40 to $38,892--a move allegedly intended to boost profits for Questcor. In addition to the suits for its bribery scheme, Mallinckrodt has also faced accusations from the government for Questcor’s charitable foundation activities between 2010 and 2014.  As the government alleges, Questcor has been using its charitable foundation as a means of paying illegal kickbacks to market its drug as free to doctors and patients.  

The Importance of Legal Review

These cases highlight the importance of legal and regulatory on promotional review teams, particularly as a means of preventing millions of dollars in fines and potential jail time.  Regulatory attorneys offer reviews of company transactions to ensure compliance, and can also investigate how payment is affecting patients and doctors, whether speakers are necessary, and if a drug’s cost is fair market value.  In addition to all of these services, legal is also able to evaluate proposed market plans, and determine whether or not they are part of a bigger scheme.

Alzheimer’s and Snake Oil Salesmen

The U.S. Food and Drug Administration (FDA) and the Federal Trade Commission (FTC) took definitive action in February 2019 when they filed warning letters against companies making false claims about their products’ ability to treat dementia.  This move on behalf of federal officials was meant to prevent patients from using supplementary drugs that might interact in harmful ways with their FDA-approved medication.  Dietary supplements claiming to possess medical benefits have become a problem in the drug marketplace, particularly as consumers forego their doctor-prescribed medication in favor of supplements that do not work.

In the case of products that were being marketed as valid treatments for Alzheimer’s, there was one particular company called Gold Crown Natural Products which was a repeat offender—it was issued multiple warning letters for fraudulently claiming that melatonin and colostrum supplements provided benefits to those dealing with Alzheimer’s disease.  The primary issue with products like those being produced by Gold Crown is that dietary supplements cannot market themselves as a cure or treatment for diseases like Alzheimer’s.

What Can Federal Authorities Do?

Although it seems that the FDA should be able to put a stop to the spread of this kind of supplement, it is not as easy as it sounds.  This is because the FDA over the manufacturing and labeling of the products.  These dietary supplements are also often sold online through platforms like Facebook, Instagram, or Twitter, and these online transactions make the sale of the products hard to trace and regulate for federal authorities.  Despite the difficulties involved in regulating these supplements, the FDA managed to issue up to 40 warning letters in the past five years to companies placing these products on the market.

Why Does it Matter?

Many people seem to be under the impression that dietary supplements are harmless. However, if taken in conjunction with medication, they may cause harmful side effects.  Additionally, some patients also decide to take supplements in place of FDA-approved medication, and therefore risk regressing in their treatment plan. The spread of these dietary supplements can also lead to false hope among patients, and risks harming the bond between clinician and patient.   

These types of false claims are not only harmful for the people who buy into them, but also for the advertising and sales industry as a whole, because they reduce overall trust in the system.  If people are unable to trust the claims that companies make about their products—particularly the claims made by smaller companies—then they are less inclined to buy the products being marketed.  There must be an attempt made by advertising companies to find some solid basis for their claims, otherwise consumers will remain wary about their products’ efficacy.

Stem Cell Treatments Pose Risks to Patients: FDA Investigates

Stem cell clinics have been steadily growing in number in recent years, and their popularity can be attributed to their claim that they can treat ailments not curable by traditional medicine.  This claim, however, remains poorly substantiated, and the use of stem cell therapy has drawn criticism from the FDA, which considers stem cell therapy to pose a high risk to patient health.  Despite scrutiny from the FDA, stem cell clinics seem to occupy a regulatory grey area, and continue to purport that they are not under FDA authority.

Are Stem Cell Clinics Under FDA Jurisdiction?

Stem cell clinics have attempted to sidestep FDA regulations by claiming that their procedures fall under ‘practicing medicine’ as opposed to developing a product that the FDA would then have jurisdiction over.  Some clinics have also gone on to falsely claim that they are performing research--not offering treatment options--in an effort to escape FDA oversight. Despite this, the FDA has gone on to approve certain procedures including those for blood disorders, however the vast majority of stem cell procedures remain unproven. Some examples of these unproven procedures include the extraction of stem cells through the process of liposuction and the placement of these cells in different parts of the body.  This process, according to the FDA, poses a certain amount of risk to the patient, who is in danger of injection site reactions in addition to side effects including tumors and blindness. In one instance, during a clinical trial conducted by U.S. Stem Cell, three patients lost all or most of their sight as a consequence of participating in the treatment plan—raising questions about the safety of these procedures.

FDA Regulation

The FDA has taken several measures to ensure proper regulation of these stem cell clinics.  When conducting the FDA review, for instance, investigators must show how each product will be manufactured to make sure that steps are being taken to guarantee product safety, as well as testing for potency and evaluating risks based on data taken from animal studies.  All of these steps are taken into account when determining whether or not a certain product is granted FDA approval.

The FDA sent out a warning letter in 2017 to stem cell clinics for marketing unapproved products as well as violating good manufacturing practices.  Despite these clinics’ claims that they were not subject to FDA jurisdiction, the FDA went ahead with their prosecution—indicating that the FDA considers stem cell claims a high enough risk to justify spending money for the prosecution and investigation of these clinics.

What the Future Holds

Although stem cell clinics have faced significant scrutiny from the FDA, a spokeswoman for one stem cell clinic stated that her company would continue offering stem cell treatments derived from other tissue.  It remains an ongoing struggle on behalf of the FDA to keep up with the regulation of stem cell clinics, as the industry continues to grow at an exponential pace.  At present, it seems that the FDA will continue issuing warning letters and initiating court cases against unscrupulous clinics,

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