The safety of pharmaceutical drugs is a top priority for the different regulatory authorities around the globe. It is monitored through well established set of activities that are described in the Risk Management Plan (RMP). An RMP is required by Health Canada and other global regulatory authorities as part of New Drug Submission (NDS) files. The aim of an RMP is to ensure risks of drugs are assessed periodically in post-marketing setting through implementation of Pharmacovigilance (PV) activities and risk minimization measures.
While there exist official guidelines set by Health Canada to guide Canadian MAHs draft and submit RMPs; availability of the drug in question under different jurisdictions, its use in a particular patient population, and risks identified during clinical phase are some of the factors that play an important role in the RMP strategy. Therefore, it is important to develop a comprehensive RMP allowing the MAH to continuously monitor the risk-benefit balance of the drug.
Our guest author, Elisabete Rego, MSc. – Associate Director, Local Safety Officer Canada at Alexion – AstraZeneca Rare Disease, provides further insights to the Canadian RMP requirements and considerations for MAHs to ensure their compliance to Health Canada guidelines.
Here is a summary of our discussion with Elisabete
What are main areas Canadian MAHs need to consider for marketed products with DIN when writing the RMP as it pertains to the PV activities?
When writing a Canadian RMP (which can be in the EU format, other recognized formats or a Canadian specific addendum), it is crucial to demonstrate that the planned PV activities (routine and/or additional) address the type of safety concerns associated with the MAH’s products in the Pharmacovigilance Plan section of the RMP.
Routine PV activities (such as signal detection activities, preparation of periodic summary reports to Health Authorities or monitoring of Canada Vigilance Database) may be sufficient for risks that do not qualify as important as their impact may be minimal to the risk-benefit balance of the product or when safety concerns are well characterized. However, the MAH should consider adding additional PV activities (e.g.: safety studies or registries) specially with new products where the safety profile has not been well characterized, products with serious safety concerns or to further collect data in areas with missing information.
In situations where an additional PV activity is imposed by other competent authorities, the MAH should provide a rationale why the same will not be implemented in Canada. Similarly, if additional PV activities exist in other major jurisdictions, the sponsor should specify the ones that are applicable to the Canadian context.
What are the main elements to consider for the development of RMP follow-up to fulfill commitments and updates with Health Canada?
Follow-up commitments and updates to the RMP may include those requested by Health Canada or those that the MAH deems they substantially change the Risk Management Plan or its minimization activities such as:
- When the serious safety concerns are significantly different than those described in the existing plan or warrant different measures to reduce or minimize their risks
- The MAH identifies safety concerns that require additional PV activities or changes to the risk minimization measures
- The measures that the MAH intends to take are significantly different than the existing RMP previously submitted to Health Canada
- The final study results confirm a safety risk with the product
On what basis should Canadian MAHs initiate a follow-up or an update to RMP should the product safety profile be changed (it is related to signal detection, label change, new indication …etc.)? who initiate the update?
Follow-ups or updates to RMP should be submitted for any of the reasons provided above and as soon as feasible or within the timeframe requested by Health Canada.
The updated Draft Guidance Document – Submitting risk management plans released for consultation on 17-Dec-2022 until 27-Mar-2023 describes what would warrant an update to the RMP by defining what is considered significantly different from the known risks and uncertainties with those risks as described in the existing plan. For example, increased potential for medication error or accidental exposure which can be identified upon preparation of annual summary reports or a new risk identified in an expanded target population, as a result of a new indication.
The RMP is not only a dynamic document but also a program that intends to identify and mitigate safety concerns to ensure that the benefit–risk balance of the medicine remains favorable. It involves significant cross-functional effort, so it is critical that Pharmacovigilance organizations work closely with Regulatory Affairs, QPPV officers (as applicable), Safety Scientists, Quality and even Medical Affairs. Usually, PV organizations are receivers of information from all parties so it is important that other functions understand the role of Safety in owning the RMP and implementation measures.
During a GVP audit, what are common areas of concerns regarding the overall RMP of a particular product?
Up until now, elements of the RMP have not been within scope of GVP audits in Canada (except for opioid products and COVID-19 with the Interim Order).
However, with the release of the updated Draft Guidance Document – Submitting risk management plans open for consultation from 17-Dec-2022 until 27-Mar-2023, and inclusion of RMP requirements in section C.01.700 of the Food and Drug Regulations, failure to submitting an RMP within 30 days upon request from Health Canada, may result in suspension of drug commercialization. In addition, non-compliant RMP may be subject to high risk observations during a GVP audit.
Do you see the importance of RMPs increasing in future NDS/SNDS submissions beyond what it is today?
Yes, more and more this is an area of interest as Health Canada works closely with other regulators and the need to be up to date with minimization programs requirements such as REMS in the US or EMA requirements for RMPs. Harmonization has always been sought to comply with ICH guidelines and Risk Management and Mitigation Programs are no different than other PV areas. If the safety profile of a product is not substantially different in other jurisdictions where it is approved, MAHs are encouraged to have similar mitigation plans across regions.
More importantly, some life-saving therapies may only be accessible to patients and approved by regulators because there is an RMP which ensures that serious risks that arise with these treatments are appropriately mitigated.
About Zenith PV solutions:
If you are planning to submit an NDS in Canada, Zenith PV team can support you proactively developing and writing an RMP/Canadian addendum that is aligned with your internal and global PV activities. Zenith PV can also support you writing a follow-up RMP as required.
Contact us today to discuss your needs with a senior Zenith PV partner at info@zenithpv.ca
References:
- Submitting risk management plans draft guidance document: Procedures to submit
It’s a timely article highlighting the next big area of GVP audit focus. Thank you for an elegant summary.