Feature articles over the past weeks have focused on the ability to assess and manage the benefit-risk profile of drugs, rules for updating prescription drug labels, off-label communications efforts, FDA’s role in regulating the advertising and promotion of prescription drugs, biologics and medical devices, the challenges of regulating mobile applications versus computers systems and recommendations for measuring regulatory compliance of complementary medicines. Researching and planning of clinical endpoints, including navigating through FDA’s understanding and interpretation of laws and definitions is also covered.

Benefit-Risk Management

Ensuring the benefits associated with a drug product’s use outweigh its risks is an important concern for regulators and regulatory professionals alike. Over the past decade, the ability to assess and manage the benefit-risk profile of drugs has been significantly enhanced by several important new additions to the benefit-risk management “toolkit” in addition to the inclusion of patient experience. Global risk management experts Meredith Y. Smith, Hilda W. Chan, Carmit Strauss, Kimberley Hockley and Andrea Russell provide an overview of the emerging science of “patient input” in the drug development process. Their article, “Benefit-Risk Management: the Role of Patient Input,” summarizes key, multi-stakeholder initiatives, discusses and explains forthcoming guidance from FDA and describes potential methods—both quantitative and qualitative—for collecting patient input to address specific regulatory questions concerning benefit-risk assessment and risk management across a medical product’s lifecycle.

Advertising, Promotion and Labeling

In “Pregnancy and Lactation Labeling Rule: Strategies for Updating Prescription Drug Labels for Compliance,” regulatory experts Chantal (Haber) MacDonald and Mandy Dorsey outline the process by which a sponsor can update a previously approved United States Prescribing Information (USPI) to be compliant with FDA’s Final Rule Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling (79 FR 72063) which introduced significant changes to the format of the USPI for prescription drug and biological products. The authors outline steps for approved labeling to contain current, complete and unambiguous pregnancy and lactation information for the benefit of both prescriber and patients.

Drug advertising in Canada is complex with many different rules and regulations for advertising prescription and non-prescription drugs as well as specific regulations for advertising aimed at healthcare providers (HCPs), patients and consumers. In addition, Canada also has a unique, voluntary self-regulatory advertising pre-clearance mechanism in place offering an option for prescription drug advertising materials to be reviewed and approved by an independent agency prior to their use.

Regulatory expert John Wong discusses Canadian drug advertising regulations and focuses on applicable laws from Health Canada and various other Canadian regulatory bodies. “Canadian Drug Advertising Regulations” stresses the importance of understanding what Canada considers advertising, the limitations on marketing efforts and whether healthcare product advertising is aimed at healthcare providers, patients or general consumers for companies outside of Canada who want to enter the Canadian market and advertise their products in Canada.

FDA determines whether medical products are safe and effective for their intended use(s) contingent on the agency’s review and approval of the product’s label; the primary tool used to communicate essential information for safe and effective use. Additionally, FDA plays a crucial role in regulating the advertising and promotion of prescription drugs, biologics and medical devices. Experienced regulatory managers Francis Nguyen and Frances Sousonis discuss off-label promotions and subsequent changes in related FDA guidances derived from the agency’s approaches to two First Amendment cases and recently enacted state laws regarding off-label communication. The article, “Clarifying FDA’s Off-Label Promotion Efforts,” suggests that Federal court challenges, newly enacted laws and the value of off-label information from a clinical practice and health economic perspective have pressured FDA to “fine-tune” interpretation of its regulations to make them more explicit for off-label communications.

The growth of mobile applications is a key component in the future of digital health and regulations are evolving to correspond to such technical advancements in this dynamic digital era, including new FDA guidance in which mobile applications would be regulated as Software as a Medical Device (SaMD).

Medical device experts Loganathan Kumarasamy and Stephen Amato present the challenges associated with the regulation of mobile medical applications compared to computer software. In “Regulatory Challenges in Mobile Medical Applications,” the authors identify the differences between mobile applications and computer systems to determine the practical challenges of regulating these mobile application. The article also highlights various principles that can be followed to ensure patient safety and wellness by mobile application manufacturers.

In “Australian Regulatory Framework of Over-the-Counter and Complementary Medicine” global regulatory expert Abhishek Tongia discusses Australia’s regulatory framework for Over-the-Counter (OTC) and complementary medicines as defined by the Medicines and Medical Devices Regulation (MMDR) and provides medicine-related classifications, types of postapproval changes, labeling, stability and advertising requirements. The author recommends measures for reinforcing regulatory compliance of complementary medicines.

Legal experts Robert Guzman and Clifton McCann focus on medical device regulation by FDA and medical device patent protection by the US Patent and Trademark Office (USPTO). In “Medical Device Marketing Under Substantial Equivalence—FDA Clearance and USPTO Patent Considerations ,” the authors state most companies operating within the medical device space do not provide for sufficient interaction between those responsible for FDA approval and those responsible for patent protection. Because a “leak” of information about an invention during the FDA approval process before a patent application is filed can destroy any chance for meaningful patent protection, the authors suggest medical device companies should work to promote a better understanding of patent objectives and risks among those responsible for FDA approval, as well those responsible for patent protection.

Regulatory Intelligence Tools

Endpoints are measures intended to reflect the effects (efficacy endpoints) or safety (safety endpoints) of a drug or device. One of the critical parts of assembling a product’s “Strategy Playbook” or “Clinical Development Plan” is the researching and planning of clinical endpoints from Phase 1 through 3, including navigating through FDA’s understanding and interpretation of the laws and definitions. In “The Regulatory Strategist Toolbox: Clinical Endpoint Analysis Tools,” regulatory intelligence expert Meredith Brown-Tuttle explains how to research endpoints, including tools to research them, how to organize the information and how to present the intelligence back to the team.

Research

Regulatory professional Max Sherman takes a look at the intellectual benefits of a “liberal arts” education in “Grammar, Logic and Rhetoric: the Trivium.” He focuses on three foundational elements and reviews ways in which the skills learned by studying “the Trivium” could benefit regulatory professionals in performing their tasks.

Feature Articles Coming Throughout October

October articles will feature the US regulatory landscape, including comparability bridging studies for combination products, the process for performing GMP audits, an update on the regulatory progress of biosimilars, FDA’s Small Business and Industry Assistance Program, 21st Century Cures Act and acceleration of device approval and theoretical perspectives of technology for regulatory science. Look for these feature articles and more on advertising, promotion and labeling regulations and best practices throughout October. If you have a suggestion for a feature article, contact me at ghall@raps.org.