Pharmacovigilance.

Medicinal products are monitored after they are put on the market to assure that adverse drug reactions (ADRs) are

detected, assessed, and addressed.  US FDA studies (2018) suggest that 6.7% of hospitalised patients have a serious adverse drug reaction with an estimated 2,216,000 serious ADRs in hospitalised patients, causing over 106,000 deaths annually in the US.

In the EU, the objective of pharmacovigilance is to protect public health, and this falls within Article 152(1) of the Treaty. Pharmacovigilance legislation[1] makes companies focus on EU compliance and accountability.

The profile of the regulatory function and in-house legal counsel within pharmaceutical companies in the EU and the US has grown exponentially over the past ten years. Unless regulatory and contractual affairs are in order, and unless there is proper legal and regulatory input into the company’s strategy development, the core business of the pharmaceutical industry could be seriously compromised.

The high priority given at EU level to pharmacovigilance cannot be stressed enough. Pharmaceutical legislation places considerable emphasis on drug safety and enhanced pharmacovigilance obligations to protect the patient.

The most common Pharmacovigilance compliance failures and challenges that the pharmaceutical industry faces include:

1. Misunderstanding terminology and requirements;
2. Poor or incomplete SOPs;
3. Poor inter-company communication;
4. Failure to train representatives and healthcare professionals;
5. Inefficiency and delay;
6. Failure to provide regular review and audit of data and procedures;
7. Inadequate follow-up of reports;
8. Failure to make liaison arrangements and connect licensees, distributors, joint ventures, partners and other third parties’ obligations;
9. Failure to learn from experience.

 

The legal consequences of failure to meet the requirements can be:

1. Regulatory;
2. Civil;
3. Criminal

The “Responsible Person” does not insulate other officers of the company.  Senior officers of the company of sufficient level of authority and having some degree of responsibility, involvement and/or knowledge can generally be made subject to enforcement proceedings. A loss of credibility with regulatory authorities can also be a serious business concern.

The objective of European Pharmacovigilance legislation is achieving proper risk management through the recording of suspected adverse drug reactions and data collection from all stakeholders. The latest EU regulation imposes legal obligations on the responsible parties. Biosimilars, which are biologic medicines, require additional monitoring. The continuous benefit–risk assessment is an obligation of all marketing authorisation holders.

According to pharmaceutical legislation, risk management plans are the starting point and are included in detail in the Marketing Authorisation Applications.  An adequate risk management system must be in place.  It explains how the MA holder intends to manage risk.  A summary of the whole pharmacovigilance system is required and the full details of the pharmacovigilance system are kept by the MA applicant/holder in the pharmacovigilance master file.

The European Medicines Agency has issued a notice to stakeholders on the regulatory expectations of medicinal products for human use (Pharmacovigilance Section 4)[2] to address challenges arising from the COVID-19 pandemic, with a particular focus on crucial medicines for use in COVID-19 patients.  The guidance covers pharmacovigilance inspections, system audits, and corrective and preventive actions (CAPAs).

 

We offer the following Pharmacovigilance services:

• Negotiation, drafting, and review of complex commercial contracts establishing clear Pharmacovigilance obligations and cooperation between the Marketing Authorisation Holder (MAH), business partners, and commercial stakeholders;
• Drafting, design, review, and update detailed documents providing Standard Operating Procedures (SOPs) to achieve regulatory compliance and minimise civil law and product liability claims;
• Advise on the interpretation of local pharmacovigilance regulations and application of different laws to comply with EU legislative texts;
• Advise on the risk-management plan (RMP)/pharmacovigilance plan, taking into account the risks identified during product development, the potential risks identified, and how those risks will be addressed and mitigated after authorisation of the product;
• Analyse and advise on the multiplicity of complex legal requirements imposed by different national competent authorities on global pharmaceutical companies;
• Ensure efficient exchange of relevant product and market information and regulatory data between separate legal personalities within a corporate group that have products in common with different jurisdiction, operations, and organisation;
• Ensure correct procedures are in place for a review of a totality of the ADRs received;
• Provide bespoke training to company officers and representatives about pharmacovigilance requirements, license agreements, legal obligations, the impact of pharmaceutical law on business operations; and dispute resolution.
• Analyse reports and follow-up information with knowledge of the approach to reporting that is characteristic of the health professionals in Malta, other EU Member States, and the US;
• Draft and communicate information to the national competent authorities in relation to the evaluation of the risk-benefit balance of medicinal products, including appropriate information on Post Authorisation Safety Studies (PASS) and Post Authorisation Evaluation Studies (PAES);
• Advise on the educational training of healthcare professionals and Direct Healthcare Professionals Communications (DHPC) on the safety and efficacy of medicinal products, in compliance with advertising regulations;
• Advise on packaging compliance, particularly for products that require additional monitoring;
• Conduct and coordinate independent external audits of pharmacovigilance compliance.

 

[1] The laws and guidance documents covering pharmacovigilance obligations in Malta include:

1. The Medicines Act (Chapter 458 of the Laws of Malta)
2. Pharmacovigilance Regulations 2012 (S.L.458.35 as amended)
3. Codified Directive 2001/83/EC as amended by Directive 2010/84/EU and Directive 2012/26/EU
4. Commission Implementing regulation 520/2012
5. Clinical Trials New Regulation No 536/2014 on clinical trials on medicinal products for human use
6. Clinical Trials Regulations 2004 (S.L.458.43 amended by L.N 248 of 2007)
7. Parallel Import of Medicinal Products Regulations (S.L.458.40 amended by L.N 291 of 2014)
8. Medicines Authority Guidance notes.

[2] https://ec.europa.eu/health/sites/health/files/human-use/docs/guidance_regulatory_covid19_en.pdf