We live in a fast-changing world accelerated by the digital revolution, and healthcare has not escaped the change. Yet, for the consumer health industry, keeping pace is not always easy, especially when trying to integrate innovative research methodologies when current regulations still need to be adapted to accept new ways of providing evidence.

As a result, many Consumer Health companies are still relying on traditional ways of innovating - such as standard RCTs for new claims or products, basic line extensions such as pack size increases for existing products - in the highly regulated OTC environment.

However, as the healthcare continuum re-orientates around the consumers – who are generating countless amounts of health data through wearables and other connected devices - identifying country dynamics, landscapes and requirements has become a priority in data generation.

In the pharma space, patient-reported outcomes (PROs) now play a crucial role in understanding a product´s benefit and in addition data deriving from digital health apps and wearables are increasingly used to measure and analyze patient experience. In line with that shift, regulators such as the US FDA encourage companies to provide data summaries, real world evidence (RWE), and real-world data (RWD) to support approval of new indications, including a required statement on patient experience data.

Yet, the diversity of products in the self-care space - ranging from OTC medicinal products to other categories like health supplements and dermocosmetics – poses a challenge when it comes to developing regulatory frameworks that can embrace new research methodologies, such as real-world data (RWD) and real-world evidence (RWE).

Are OTC frameworks fit for purpose?

OTC medicines are regulated in a similar way to prescription products. However, from the product and the data requirements perspective there can be significant differences. Most of the APIs and products have been on the market for a long time – even for several decades in many cases. Safety and efficacy were generally proven years ago and the benefits in the real-world setting are widely accepted.

In this way, OTC medicine regulations should be treated differently from the prescription ones. This is especially true when it comes to the integration of scientific evidence derived from new types of real-world consumer studies used to develop new consumer-relevant claims.

Almost five years ago, the UK industry association, the PAGB published a report that stated that the “system to regulate consumer health products needs to be fit for its purpose and that means it needs to differ from the system to regulate prescription products”.

“A balanced benefit risk evaluation for marketing authorizations is essential for the full potential of self-care to be reached. This means accepting that non-prescription medicines do not enjoy patent protection and by their nature have their safety and efficacy established by scientific studies that were not conducted to today’s standards but for the most part have been verified by many years of safe and effective use in the real world.”ⁱ

This raises the question why haven’t OTC frameworks been adapted to incorporate these years of safe and effective real-world use?

One reason could be that while the processes for gathering and integrating RWD and RWE into prescription medicine approvals has focused on sources and data deriving from healthcare data bases, patient registries, pharmacy, and health insurance databases etc, for consumer health products such RWD is usually not easily available.

However, consumer experience data collected directly in a retrospective or prospective way, and data deriving from new technologies such as smartphones and wearables, can play an important role in gathering new types of information and outcomes complementing data from previous clinical trials. Such data helps to understand better the consumer health journey and the value of a product, and in a small number of cases is already being used.

There are already examples of consumer health companies using these processes – primarily to enhance promotional claims - for example, Bayer Consumer Health and IQVIA Consumer Health in Thailand collaborated to generate compelling claims backed by real-world evidence to form the backbone of a hit television advertisement for the nappy-care brand Bepanthen - but it has yet to become common.

Highlighting the benefit of adopting these methods, Sheryl Tan, Head of Medical, Bayer Consumer Health APAC pointed out that: “For Bayer, we see these new technologies as enhanced ways to validate our existing clinical science and better relate the benefits to our consumers. We also seek to bring value both ways – for consumers to understand their health better, and for companies like Bayer to understand their needs better.

Regulation has yet to catch up

There is a case to be heard that OTC regulations have yet to catch up with the technological developments of the past decade.

For OTC medicinal products most “label claim” relevant evidence, at first glance, is based on randomized controlled Trials (RCTs) – the traditional industry gold standard to ensure compliance with regulatory rules that are more or less comparable to the prescription medicine process – and is a must in many countries where superiority claims are made for indications on a license/pack and in advertising.

While RWD is becoming more accepted for health supplements/food supplements across a number of markets, predominantly in advertising to consumers, RWD sources accepted in OTC frameworks are limited, and the more innovative study approaches needed to generate such data are not yet applied broadly enough to give regulators a base to build from. This includes consumer surveys targeted to learn more about the perceived product benefits in a real-world context and the integration of digital technologies such as apps and wearables.

Regulators are progressing, but they are not there yet. For example, while the US FDA has defined a framework for Real-World Evidence programs, non-medicinal products in the self-care space are not really covered.

While in July last year, the Association of the European Self-Care Industry, the AESGP, urged the European Commission to use its new pharmaceutical strategy to recognize the “high potential for RWD/RWE for non-prescription medicines, throughout their lifecycle,” and not limit the new strategy to “just supporting the development of medicinal products for unmet medical needsⁱⁱ.”

Janie Heywood, Head of Consumer Health Regulatory Affairs, APAC, at Bayer Consumer Health, APAC noted that “traditionally, regulators have been quite conservative and prescriptive in the OTC registered medicines space, but in some markets, including the US, UK and some countries in Asia-Pacific, health authorities are more open to working with industry to help drive innovation and broaden access to medicines and healthcare products in certain categories.”

In the US, the OTC Monograph reform law under the CARES act for pandemic relief is an important regulatory step for the US Food and Drug Administration (FDA) to significantly increase the capacity and expertise in the Office of Non-Prescription Drug Productsⁱⁱⁱ, while also reforming the system – which covers about 60% of OTC medicines – to encourage more innovation by providing a pathway to amend monographs and potential incentives to reward investment in new products.

The FDA is also supporting RWE approaches^iv to extend the understanding of a product in terms of efficiency and safety, having announced in 2018 efforts to transform its approach to digital health, including tools such as digital biomarkers, to help to make drug and device development more predictable, efficient, and more reflective of patients’ real-world experience.

Meanwhile, in Asia Pacific, there are active dialogues taking place within regional regulators. For instance, in South Korea, there are major improvements being discussed to expand OTC monograph, while in Japan, a reform plan refers specifically to promoting Rx-to-OTC switches and self-medication with the establishment of evaluation committee for switch OTC candidates, where candidates requested by patients, pharmacists, companies, and others are evaluated for acceptability as a switch OTC^v.

However, the differing pace of change and a lack of global harmonization across all aspects of OTC medicines regulation also poses an issue for integrating new R&D processes into the consumer health field in general.

“If you take Europe as an example,” Heywood pointed out, “harmonization of regulations across medicines and medical devices and mutual recognition had reduced industry burden. However, even though regulators outside the EU look to the EU we still do not have mutual acceptance of evaluation reports or mutual recognition such that a product approved for use in France still has to undergo rigorous evaluation before approval in developed markets such as Australia.”

“There have been at least 2 recent attempts to have a joint regulatory agency between Australia and New Zealand or indeed Trans-Tasmin mutual recognition, but this has never come to fruition,” Heywood added. “This can lead to the different product classifications, different labels on exactly the same product, essentially creating a trade barrier because different products/labels are not commercially viable for a smaller market like New Zealand even for multi-nationals.”

“There is an opportunity for governments to drive mutual recognition, greater harmonization,” Heywood said, “with COVID-19 being a very public example of how regulators have shown they can be more flexible e.g. introducing the provision for electronic submissions in countries where previously it was not permitted.”

Collective effort to accelerate innovation

There is a case to be made for regulatory acceptance of new evidence built on a foundation of big data, consumer, and HCP insights. There is also potential to create structured guidance by geographies on advertising and related claim substantiation rather than full complex clinical analyses for established formulations.

So, should OTC manufacturers be more pro-active and engage more with regulators to make the next step in RWE for self-care and consumer health together? Define some quality standards on how RWE can be created, collected, and analyzed?

The short history of RWD / RWE applied in the pharma industry demonstrates that regulators are open to new ways to generate evidence for the benefit of all stakeholders, especially patients^vi.

It will take a joint industry effort to usher in the era of consumer health, with industry and regulators working closely together to:

• Develop a common understanding of what RWD/RWE means, which quality parameters need to be applied and how it can be used for Consumer Health per regulatory category and region
• Develop and apply new study approaches demonstrating the value of filling the data gap between RCTs and the real-world product usages
• Integrate new data sources informing about perceived consumer benefits and consumer behavior
• Translate outcome of such studies into more relevant product claims and information to help consumers make the best decisions.

We believe this will eventually result in consumer-centered innovation, with relatable and relevant products and claims based on strong, consumer-derived evidence, enabling access and truly empowering consumers to take charge of their healthcare.

i. https://www.pagb.co.uk/content/uploads/2016/06/RB-EIU_Consumer_Health-Report.pdf
ii. https://hbw.pharmaintelligence.informa.com/RS150206/Rx-To-OTC-Switch-And-RWE-Key-To-Creating-Crisis-Proof-European-Medicines-System
iii. https://www.raps.org/news-and-articles/news-articles/2020/4/otc-monograph-reform-is-now-law-whats-next
iv. https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence
v. http://www.apsmi.net/newsletter/data/2020_01.pdf
vi. https://www.fda.gov/media/120060/download; https://www.ema.europa.eu/en/documents/presentation/presentation-real-world-evidence-rwe-introduction-how-it-relevant-medicines-regulatory-system-emas_en.pdf; Bolislis WR, Fay M, Kühler TC. Use of Real-world Data for New Drug Applications and Line Extensions. Clin Ther. 2020 May;42(5):926-938. doi: 10.1016/j.clinthera.2020.03.006. Epub 2020 Apr 25. PMID: 32340916.

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