European Regulatory Roundup: Roche Escapes Penalty for Breaching EU Pharmacovigilance Rules (21 December 2018)

Posted 21 December 2017 By Nick Paul Taylor

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Roche Escapes Penalty for Breaching European Pharmacovigilance Rules

Roche has escaped punishment over its failure to comply with pharmacovigilance requirements. The European Commission showed leniency after concluding Roche's response to its shortcomings made the imposition of a financial penalty unnecessary.

The genesis of the case dates back to 2012, when the Commission asked the European Medicines Agency (EMA) to investigate allegations that Roche had failed to comply with pharmacovigilance requirements. The allegations centered on 19 centrally authorized products. EMA confirmed shortcomings at Roche, particularly with the handling of pharmacovigilance information derived from market research and patient support programs, both inside and outside the European Union.

That led to the initiation of an infringement procedure later that year and, four years after that, to the submission of a final EMA report to the Commission.

The case is the first initiated under the Penalty Regulation. That means the Commission has the power to impose financial penalties on Roche. These penalties are intended to ensure marketing authorization holders fulfill their obligations. In the case of Roche, this was deemed unnecessary as the company had already acted on the findings. The Swiss pharma outlined its response in a statement to the Commission.

"Roche accepted all the inspection findings. It took them extremely seriously and fully understands the EMA's and Commission's concerns. It has worked diligently to remediate the deficiencies as quickly as possible and also to enhance the company's medical compliance and pharmacovigilance systems to prevent any recurrence," Roche wrote.

The company went on to say, "Its efforts to enhance its systems and to maintain the trust of all stakeholders must continue."

Yet the Commission's comments suggest Roche now has its house in order. The Commission said Roche "fully and explicitly recognized" the inspection findings and took near-term remedial actions, while also making a long-term commitment to the improvement of its operation. The Commission thinks the actions address the failings identified in the inspections and "provide sufficient assurances that the inspection findings should not occur again in the future."

The final fact in Roche's favor is the status of the products that sparked the initial investigation. The Pharmacovigilance Risk Assessment Committee (PRAC) has completed its evaluation of periodic safety update reports submitted by Roche and found no need to change the terms of the marketing authorizations.

"It appears that the previously unassessed information did not have any impact on the benefit-risk profiles of the products concerned. There is hence no actual risk to public health or patient safety," the Commission wrote.

Commission Statement

EMA Revises Anti-Fraud Strategy in Light of Experience of Recent Years

EMA has revised its anti-fraud strategy. The agenda for 2018 to 2020 builds on the work done by EMA in recent years to create a fraud-proof environment within the agency by raising awareness of the threat and establishing reporting processes.

When EMA established its original anti-fraud strategy in 2014, the focus was on developing a culture and capabilities that prevent and identify malfeasance. That done, EMA's focus has shifted to maintaining the gains already made while becoming more proactive and expanding its efforts to third parties working with the agency.

Broadly speaking, the objectives are variations on those laid out in the original. These recurring goals include EMA's commitment to maintain an anti-fraud culture and a system for reporting irregularities, the development of which was triggered by the original strategy.

The maturation of EMA's capabilities has led it to revise its approach to achieving the objectives. In the coming years, EMA will expand its training program to cover contractors, who are potentially a backdoor into the agency's confidential materials. EMA also plans to create a register for internal whistleblowing.

In other areas, EMA has changed its language while retaining some of the intent. Rather than focus one objective on favoritism in recruitment and procurement, as it did in the earlier strategy, EMA wants to "strengthen measures for detection of suspicious behaviors and deterrence."

To achieve this objective, EMA plans to perform proactive random verifications in cooperation with heads of divisions and put revisions to its conflict of interest policies through impact assessments.

Brexit may hinder the anti-fraud agenda, both in terms of its effect on EMA's non-core activities and the new risks created by the agency's relocation. EMA has already cut training programs in response to the strain placed on its operations by Brexit. The agency expects to cut or delay more activities as the full impact of its relocation starts to hit home.

The relocation also creates its own fraud threats. EMA plans to run audits "in light of the additional operational concerns stemming from the agency's relocation in 2019 to a new host member state."

EMA Strategy

CVMP Establishes Position on Ethical Use of Animals in Veterinary Drug Development

An EMA committee has set out its position on the ethical use of animals in veterinary medicine testing, development and production. The statement confirms drug developers and manufacturers must follow EU animal welfare rules regardless of where the work is being carried out.

It makes no difference to EMA's Committee for Medicinal Products for Veterinary Use (CVMP) whether the work is being performed in Mumbai or Milan. If the product is destined for the EU market, its development, testing and manufacture must comply with EU rules and ethical values relating to animal welfare.

The statement focuses in on "certain animal models of disease or pain" to show how attitudes to welfare can differ between countries inside and outside the EU. CVMP has had concerns about the use of such models recently on the grounds that the likely harm to the animal may outweigh the expected benefits.

CVMP cites the declawing of cats as an example of a procedure that may fail its harm-benefit calculation.

"The procedure provides no identifiable benefit to the cat but such animals behave differently to intact animals, will suffer pain in the immediate post-surgical period and may suffer chronic effects or complications," CVMP wrote.

CVMP Statement

Gates Foundation, WHO Join With MHRA to Improve Global Drug Safety

The United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) has entered into a $1.3 million partnership to improve drug safety monitoring in low- and middle-income countries.

MHRA has partnered with the Bill & Melinda Gates Foundation and the World Health Organization (WHO) on the initiative, which is called Project Smart Safety Surveillance or Project 3-S for short. WHO and the Gates Foundation set up the project to help countries assess and manage the risks posed by new medical products. MHRA will provide its regulatory expertise to the countries.

The need for such support stems from the disconnect between the maturity of the regulatory systems in many low- to middle-income countries and the novelty of the drugs and vaccines set to be sold in their jurisdiction. WHO and the Gates Foundation foresee a wave of new interventions against diseases such as HIV and malaria and a lack of infrastructure to monitor their effects.

WHO has made some strides through its Program for International Drug Monitoring, but it and its collaborators think more tools, training and capacity are needed to adequately monitor the risks of new products. The consequences of failing to provide these resources could be severe. If adverse events go unchecked, the public could lose trust in a product, thereby limiting uptake.

In an attempt to avoid such a scenario, the partners will run three pilot programs over the next three years.

MHRA Statement

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Categories: Biologics and biotechnology, Drugs, Veterinary products, Postmarket surveillance, News, Canada, EMA, EC, MHRA, WHO

Tags: EU Regulatory Roundup, Roche, Gates Foundation

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