Life Science Compliance Update

January 18, 2017

FDA Releases Draft Guidance for Medical Product Communications Consistent with FDA-Required Labeling


The United States Food and Drug Administration (FDA) released a new draft guidance that provides information for medical product manufacturers, packers, and distributors, on how FDA evaluates firms’ medical product communications – including promotional materials – that present information not contained in the FDA-required labeling for the product, but that is consistent with such required labeling.

Various medical product firms have told the FDA that they would like to communicate data and information about the approved/cleared uses of their products, including information not contained in their products’ FDA-required labeling. As a result, the FDA issued this draft guidance for all drugs and devices, including those that are licensed as biological products, and animal drugs.

Because a communication that is consistent with a product’s FDA-required labeling could nonetheless misbrand the product and subject a firm to enforcement action if the representations or suggestions made in the communication are false or misleading, this guidance also provides general recommendations for conveying information that is consistent with the FDA-required labeling in a truthful and non-misleading way, as well as examples to illustrate these concepts. Interestingly, missing from the guidance document is any mention of off-label communications.

If a firm’s communication is consistent with the FDA-required labeling, that communication alone is not viewed by FDA as providing evidence of a new intended use. Further, FDA does not view a communication that is consistent with the FDA-required labeling as failing to comply with the Federal Food, Drug, and Cosmetic Act’s (FD&C Act) requirement that a medical product’s labeling bear adequate directions for use, based solely on the fact that it presents data and information that are not reflected in the product’s FDA-required labeling.

Examples of Information that Could Be Consistent with FDA-Required Labeling

The following examples are listed as some of the examples the FDA provides of information that could be consistent with the FDA-required labeling.

  • Information based on a comparison of the safety or efficacy of a medical product for its approved/cleared indication to another medical product approved/cleared for the same indication (e.g., a firm’s communication provides information from a head-to-head study indicating that its drug that is approved to treat high blood pressure in adults has superior efficacy to another drug that is also approved to treat high blood pressure in adults);
  • Information that provides additional context about the adverse reactions associated with the approved/cleared uses of the product reflected in the product’s FDA-required labeling (e.g., the FDA-required labeling for a product identifies nausea as a potential adverse reaction and further indicates the product can be taken with or without food. A firm’s communication about the product provides information about how taking a product with food might reduce nausea);
  • Information about the long-term safety and/or efficacy of products that are approved/cleared for chronic use (e.g., a firm provides post-marketing information for its product, which was approved/cleared for chronic use based on 24-week study data, regarding persistent safety and/or efficacy over 18 months);
  • Information concerning the effects of a product that comes directly from the patient (i.e., patient-reported outcomes) when the product is used for its FDA-approved/cleared indication in its approved/cleared patient population (e.g., a firm’s communication provides information concerning patient compliance/adherence, or a firm’s communication provides information about patients’ perceptions of the product’s effect on their basic activities of daily living); and
  • Information that provides additional context about the mechanism of action described in the FDA-required labeling (e.g., the FDA-required labeling for a drug product indicates it exerts its effects by binding to a certain receptor, and a firm’s communication provides additional information about the product’s selectivity for that receptor).

Examples that Are Not Consistent with FDA-Required Labeling

The FDA also included some general types of information that they do not consider to be consistent with FDA-required labeling, some of which are below.

  • Information about the use of a product to treat or diagnose a different disease or condition than the product is approved/cleared to treat or diagnose (e.g., a product is approved/cleared to treat cardiovascular disease, and a firm’s communication provides information about using the product to treat diabetes);
  • Information about the use of a product to treat a different stage, severity, or manifestation of a disease than the product is approved/cleared to treat (e.g., a product is approved/cleared only to treat severe asthma, and a firm’s communication provides information about using the product to treat patients with mild asthma);
  • Information about using a product through a different route of administration or in a different tissue type than the product is approved/cleared for (e.g., a product is approved only for intramuscular injection, and a firm’s communication indicates the product can be injected intravenously); and
  • Information about the use of a product in a different dosage form than what is set forth in the FDA-required labeling (e.g., the product’s approved dosage form is a capsule, and a firm’s communication provides information about use of the product as an oral solution).

FDA Consideration Recommendations

The way a firm presents information that is consistent with the FDA-required labeling (including the express and implied claims made and the overall impression created by the communication as a whole) affects how the information is understood. The following are some high-level recommendations for firms to consider when developing their presentations of information that is consistent with the FDA-required labeling to help ensure the presentations do not mislead the applicable audience(s):

  • Any study results or other data and information that are relied upon to support a firm’s communication should be accurately represented in the communications. Moreover, material aspects of study design and methodology for any studies relied on should be clearly and prominently disclosed in firms’ communications to allow audiences to accurately interpret the information (e.g., type of study, study objectives, product dosage/use regimens, controls used, patient population studied), and material limitations related to the study design, methodology, and results should also be disclosed in a clear and prominent manner.
  • The communication should accurately characterize and contextualize the relevant information about the product, including by disclosing unfavorable or inconsistent findings. For example, if a firm presents efficacy results from a post-marketing study of its product that evaluated the effect of the product on two different endpoints, such as overall survival and progression-free survival, and the product failed to demonstrate an effect on one of these two endpoints, the firm should disclose this in the communication, rather than selectively presenting only the positive efficacy results.
  • For communications that present data or information that is not in the FDA-required labeling, but where the FDA-required labeling contains other data or information related to what is being represented/suggested in the communication, the communication should also include the data or information from the FDA-required labeling to provide the audience with appropriate context. For example, if a communication provides post-marketing information about the types and rates of occurrence of adverse events that have been observed in practice, the communication should also include information from the FDA-required labeling about the types and rates of occurrence of adverse reactions observed in clinical trials to provide context.

The guidance document also provides several examples for applicable audiences to review, and to determine if their situation is similar. The examples also provide a bit of extra insight into FDA’s thought process and goal with the guidance document. In general, guidance documents do not establish legally enforceable responsibilities. Instead, they describe the Agency’s current thinking on a topic and should be looked at only as recommendations, unless there are specific regulatory or statutory requirements cited.  

September 19, 2016

New Rule and Guidance Issued on Clinical Trials


Clinical trials are one of the most visible components of the biomedical research field, in part due to the way they directly engage human participants. Clinical trials have done a lot of good, providing advances in diagnosis, treatment, and prevention, but there are still large challenges. As such, changes are always needed to reflect science and society’s movement to increase efficiency, accountability, and transparency in clinical research.

Health and Human Services Final Rule

In an effort to make information about clinical trials more widely available to the public, the United States Department of Health and Human Services (HHS) issued a final rule that specifies requirements for registering certain clinical trials and submitting results information to The final rule expands the legal requirements for submitting registration and results information for clinical trials that involve drug, biological, and device products regulated by the Food and Drug Administration (FDA).

The requirements found within the rule generally apply to the “responsible party,” typically the sponsor of the clinical trial or designated principal investigator. The rule lays out a process for determining who the rule applies to, and which studies are considered “applicable clinical trials.”

Requirements under the final rule apply to most interventional studies of drug, biological and device products that are regulated by the FDA. The requirements do not apply to phase 1 trials of drug and biological products, or small feasibility studies of device products. The final rule also specifies how and when information collected in a clinical trial must be submitted to It does not, however, dictate how clinical trials should be designed or conducted, or what data must be collected.

Responsible parties must register their trial within twenty-one days of enrolling the first participant. The rule includes specific data elements that are to be submitted upon registration. Additionally, if the product studied is available via expanded access (when a product is used outside of a clinical trial, before it is FDA approved), the responsible party shall submit information about how patients can get access to that product.

Results information from applicable clinical trials shall generally be submitted within one year after the trial’s primary completion date. Submission of results information may be delayed, in certain circumstances, for up to two additional years for trials of products regulated by the FDA that are unapproved, unlicensed, or uncleared.

The type of information submitted will consist of “tables of information summarizing: 1) participant flow information, 2) demographics and baseline characteristics of the enrolled participants, 3) primary and secondary outcomes, including results of any scientifically appropriate statistical tests, and 4) adverse events.” As part of adverse events information there will be a table for all-cause mortality. The information will be submitted in aggregate, with no personally identifiable information. The rule requires responsible parties to update the information annually.

The final rule will be effective January 18, 2017. As of that date, will allow responsible parties to comply with the rule; there is a ninety-day grace period for responsible parties to come into compliance with the requirements of the rule.

National Institutes of Health Policy Guidance

The National Institutes of Health (NIH) is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is the largest public funder of clinical trials in the United States. With such investment comes great responsibility. As such, NIH must work to ensure supported trials: investigate a mission-relevant question of high priority, do not duplicate previously conducted trials that do not need replication, and have the highest likelihood to advance knowledge and improve health.

NIH has launched a new effort to improve the quality and efficiency of clinical trials. These initiatives will reengineer the process by which clinical investigators develop ideas for new trials, how NIH reviews and selects clinical trials for support and oversees the progress of the research, and how results and aggregate data are shared broadly and rapidly.  

As part of the aforementioned initiatives, NIH issued a policy on the same day as the HHS final rule, in an attempt to promote broad and responsible dissemination of information from NIH-funded clinical trials through The policy establishes the expectation that investigators that conduct clinical trials funded at all by NIH will ensure that the trials are properly registered and that results information of the trials are submitted to

The policy, similar to the rule, requires applicable clinical trials to be registered in no later than twenty-one calendar days after the enrollment of the first participant.

Applicants and offerors seeking NIH funding will be required to submit a plan for the dissemination of NIH-funded clinical trial information that will address how expectations contained within the policy will be met.

The new NIH policy applies to all NIH-funded trials, including phase 1 clinical trials of FDA-regulated products and small feasibility device trials, as well as products that are not regulated by the FDA, such as behavioral interventions.

The policy will take effect January 18, 2017. Failure to comply with the terms and conditions of the policy may result in enforcement actions, including termination.

FDA and NIH Comments

“When people participate in clinical trials, they are volunteering to create generalizable knowledge to help others in the future and we want their participation honored by ensuring that the existence of trials and their results are available to all patients and their healthcare providers, as well as researchers,” said FDA Commissioner Robert M. Califf, M.D. “The FDA will help ensure compliance with these new requirements so that patients and providers can have confidence in and access to significantly more clinical trial information, and researchers can improve clinical trial focus and design.”

“Access to more information about clinical trials is good for patients, the public and science,” said NIH Director Francis S. Collins, M.D., Ph.D. “The final rule and NIH policy we have issued today will help maximize the value of clinical trials, whether publicly or privately supported, and help us honor our commitments to trial participants, who do so much to help society advance knowledge and improve health.”

A summary table of both the final rule and new guidelines can be found here.

August 01, 2016

PhRMA and BIO Release Drug Maker Communication Guidelines


On Wednesday, July 27, 2016, the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO) released guidelines for drug makers’ communications with other health care professionals about their products.

The guidelines encompassed nine principles aimed at improving relationships between biopharmaceutical companies and other players in the health care industry, calling on the Food and Drug Administration (FDA) to clarify what information biopharmaceutical companies can share in addition to approved labels. The principles focused on three main areas, commitment to: science-based communications, providing appropriate context about data, and accurately representing data.

According to the guidelines,

"To exercise sound medical judgment in treating patients, health care professionals must understand the full range of treatment options, including both established and emerging information about available medications. Biopharmaceutical companies are uniquely positioned to help health care professionals achieve the best outcomes for patients, because companies can provide timely, accurate, and comprehensive information about both approved and unapproved uses of the medications they research, develop, and bring to patients. PhRMA, BIO, and their members believe that the availability of a wider range of truthful and non-misleading information can help health care professionals and payers make better informed medical decisions for their patients, which in turn will benefit patients."

The principles are as follows:

  1. Commitment to Accurate, Science-Based Communications
  2. FDA-Approved Labeling is a Primary Source in Sharing Information with Health Care Professionals About Medicines
  3. Companies Should Provide Scientific Substantiation if Shared Information is Not Contained in FDA-Approved Labeling
  4. Additional Science-based Information from Sources Other Than FDA-Approved Labeling Helps Health Care Professionals and Payers Make Informed Decisions for Patients
  5. Communications Should Be Tailored to the Sophistication of the Intended Audience
  6. Science-based Information About Alternative Uses of Medicines Can Improve Health Care Decision-Making
  7. Communicating with Payers About New Medicines and New Uses of Approved Medicines Facilitates Patient Access Upon Approval
  8. Real-World Evidence Based on Patient Experience and Pharmacoeconomic Information Can Improve Understanding of Health Outcomes and Costs
  9. Commitment to Share Information Published in Scientific or Medical Journals

The principles report from PhRMA and BIO goes on to illuminate how the responsible sharing of information, including the following categories, can improve patient care and the efficiency of the health care system:

  • Data from randomized, controlled clinical trials that evaluate pre-specified endpoints under a clearly defined analysis plan.
  • Post hoc analyses, including sub-population data. Randomized controlled clinical trials and observational studies often collect information on the safety and effectiveness of medicines in subpopulations, including specific gender and ethnic cohorts. If the trial has met its primary endpoint, subpopulation information may help health care professionals develop treatment strategies based on more precise safety and efficacy data for a particular cohort of patients.
  • Observational data and real world evidence, which can help clinicians understand how medicines perform across a diverse patient population outside of controlled trials. Such data may reflect prescribing patterns in different clinical practice settings, alternative doses, and differing durations of treatment, as well as comparisons between two or more therapies.
  • Pharmacoeconomic information.

Insurers and drug companies agree that further dialogue between them could help address the high costs of specialty drugs, but the current limited safe harbors are preventing those discussions happening. Perhaps these principles will help to push these communications into the realm of reality.


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