Change as constant: why pharma companies should act now in anticipation of regulatory changes: within 10 years, reporting will be risk-based across a broad spectrum of products, and pharmacovigilance procedures will be an integral part of a product's development plan. companies must anticipate [this] and build the foundation for processes that easily accommodate change.

The great visionary Buckminster Fuller once said: "To change something, build a new model that makes the existing model obsolete." Increasingly, regulatory agencies in both the US and EU are following this paradigm and constructing a new evaluative model of reporting requirements. For example, we have seen a significant focus on risk management and reporting prioritization of products based upon their risk profile. Nostrapharmus says: "industry must be prepared for this impact, not only on business operations for a traditional product portfolio, but also for medical devices, over-the-counter (OTC) drugs, cosmetics and any animal health products in their portfolio."

Regulatory Change

Both the US and EU have demonstrated an increased focus on risk-based product evaluation and reporting with recent regulatory amendments; the US has done so most notably with the Food and Drug Administration Amendments Act of 2007 (FDAAA), and the EU with proposed legislative amendments to directive 2001/83/EC and regulation (EC) 726/2004. In the US, the FDAAA establishes that a Risk Evaluation and Mitigation Strategy (REMS) may be required to ensure that benefits will outweigh the risks of a drug. In addition, the emergence of 'new safety information' or 'information necessary to ensure that the benefits of the drug outweigh the risks of the drug' may prompt the FDA to request a REMS.

The minimal strategy includes assessments, a medication guide or patient package insert, and a communication plan. Since the adoption of FDAAA, a REMS has increasingly been required for product approval, and it is anticipated that requests for post-market REMS will increase over time. With medical devices, it is anticipated that the Center for Devices and Radiological Health (CDRH) may begin demonstrating REMS-like powers in monitoring device risk.

While OTC drugs have been subject to the same reporting requirements in the EU as prescription drugs, differences did persist in the US. With the passage of the Dietary Supplement and Non-prescription Drug Consumer Protection Act, however, US l aw now mandates Adverse Event (AE) reporting for post-marketing serious adverse events associated with non-prescription OTC human drug products marketed without an approved application. This requirement extends to vitamins, herbs/botanicals, and metabolite products.

Likewise, reporting requirements for cosmetics appear to be increasing in scope and complexity. Guidance drafted by the European Cosmetics Association (COLIPA) sets forth procedures for adverse event capture, trend analysis for safety, and reporting requirements to local health authorities. In addition, proposed legislative changes to the European Cosmetics Directive (76/768/EEC) suggest the establishment of a 'responsible person' role that would maintain a list of cosmetics with substances that have raised 'serious' safety concerns. It would also ensure qualitative and quantitative composition, require that all health effect data is easily accessible to the public, and report serious undesirable health effects to an authority, along with corrective measures taken.

With regard to animal health, US products are regulated by the Center for Veterinary Medicine within the FDA. EU law will be based upon forthcoming Volume 9B for animal health, but current law focuses on guidance and directives, including the QPPV role as central to the reporting of and accountability for animal health-related adverse events. A risk management system for animal health products will be forthcoming in Volume 9B.

The proposed EU legislative amendments touch several distinct areas with regard to reporting requirements. While these are proposed changes that have not yet been enacted, Nostrapharmus notes that industry would do well to understand the implications of the proposed changes, as over time regulations typically are adopted that reflect the proposed thinking, even if the timeframe is extended. By recognizing, understanding and appreciating these new risk-influenced models, industry can act now to ensure that business operations and reporting procedures are scalable and ready to accommodate increased responsibilities.

Under the proposed legislation, market authorization (MA) applications would contain a summary of the pharmacovigilance system to include the location of the PV system master file, which is a detailed description of the PV system utilized to fulfil regulatory responsibilities. In addition, MA applications would require a risk management system proportionate to product risk. Some products of high risk would be placed on the intensely monitored product list and be subject to specialized warning requirements to be printed on packaging. In addition, the Periodic Safety Update Report (PSUR) format may also change significantly to require scientific evaluation of risk benefit balance, and would contain summaries of data relevant to risk benefit. PSURs would not contain listings of individual cases.

[ILLUSTRATION OMITTED]

With regard to AE reporting, the proposed legislation would mandate 15-day reporting for all EU source case reports. This is quite a significant change in the reporting timeframe, and companies would need to ensure that their current business processes are scalable and efficient to meet this requirement. In addition, a lower causality assessment threshold would be introduced for reporting where the causal relationship is 'a reasonable possibility,' and medication error reports would also be required. The possibility of public access to individual AE reports in Eudravigilance has also been proposed.

Some simplification measures are proposed as well. For example, patients would report suspected ADRs for medicines under intensive monitoring to the MA holder, but other drugs would be reported to the relevant national competent authority. All EU domestic reports and serious third country reports would go only to Eudravigilance. In addition, the EMEA would scan scientific literature.

Implications for Industry

As demonstrated by the recent and proposed regulatory changes, risk assessment has become an integral part of pharmacovigilance procedures. Risk assessments and mitigation plans are essentially required for products entering the market, and can be mandated for post-market products. In addition, the expanse of reporting requirements for OTC drugs, cosmetics and medical devices suggests that the industry must proactively address requirements when preparing a product for market. The COLIPA regulations would bring AE awareness and reporting to an entire industry in which

major players do not currently have pharmacovigilance procedures in place.

Why Act Now

Although some of the suggested changes are simply that suggested--at this point in time, proactive pharmacovigilance procedures will save considerable time and expense, as well as prevent regulatory non-compliance issues in the future. The need for scalable, repeatableand efficient pharmacovigilance procedures becomes paramount when a reporting timeframe is halved, or a reporting authority changed.

Nostrapharmus predicts that 'within 10 years, it is likely that reporting will be mostly risk-based across a broad spectrum of products, and pharmacovigilance procedures will be an integral part of a product's development plan. To successfully plan for these changes, companies must anticipate the way of the regulator and build the foundation now for processes that easily accommodate change.'

[e-mail].