Date: March 2005
Sponsors, usually a pharmaceutical company who develops prescription drugs, including biological drug products
Laws and Regulations:
- Protection of Human Subjects- 45 CFR Part 46
- General Administrative Requirement- 45 CFR Part 160
- Electronic Code of Federal Regulations; General Provisions, subparts A and E- 45 CFR Part 160
- Protection of Human Subjects- 21 CFR Part 50
- Institutional Review Boards- 21 CFR Part 56
- Health Insurance Portability and Accountability Act of 1996 (HIPAA) (Public Law 104-191)
- The Standards for Privacy of Individually Identifiable Health Information (the Privacy Rule)
- Guidance for Industry: Recognition and Use of a Standard for the Uniform Labeling of Blood and Blood Components (65 FR 81081)
- Guidance for Industry: E6 Good Clinical practice: Consolidation Guidance
- Premarketing Risk Assessment (Premarketing Guidance)
- Good Pharmacovigilance practices and Pharmacoepidemiologic Assessment (Pharmacovigilance Guidance)
- International Conference of Harmonization (ICH) guidance E2E: Pharmacovigilance Planning (E2E guidance)
The process of managing the benefit-risk balance takes place throughout the lifecycle of a drug. The evaluation of risk, and benefit-risk balance, starts during the early development of a drug and continues long after the drug is marketed. There are 4 steps to managing the risk: assessing the benefit-risk, developing a plan to minimize the risk, evaluating whether the plan is working, and making adjustments in the plan to ensure the drug’s maximum benefit is achieved with the lowest amount of risk to the patient.
This guidance contains the FDA’s recommendations for developing a strategic safety program or RiskMAP. Not all drugs need a RiskMAP since routine monitoring is sufficient for most. The guidance provides the FDA’s suggestions for how to determine if a RiskMAP is appropriate, and how to design and evaluate a RiskMAP. In addition, there are recommendations for how to communicate with the FDA during the development of the RiskMAP, along with when and how to report the results.
Determine When a RiskMAP is Appropriate
The decision that a RiskMAP is appropriate can be made at any time (during early development, clinical trials, and postmarketing). The sponsor should use evidence-based data when determining if a RiskMAP is needed. The evaluation of need should be ongoing as more data becomes available. The FDA also has the right to recommend a RiskMAP if they assess a need based on their review of available data.
How to Create a RiskMAP
Establish goals and objectives: A goal is the outcome the RiskMAP is trying to achieve. The objective is how the goal will be obtained. For example, the goal is that patients must not become pregnant while using the drug. The objective is to communicate to the patient that they should not become pregnant while taking the drug.
Decide which tools to use for achieving goals and objectives: A tool is the mechanism that will be used to obtain the goal and objective. The FDA recommends 3 categories of tools: targeted education and outreach (ie, patient medication guides, prominent professional or public notifications), reminder systems (ie, consent forms, limitations on refills of a product), and performance-linked access systems (ie, requiring specific lab tests to be periodically performed to establish safe use).
Assess the effectiveness of tools and the RiskMAP: To assure effectiveness, the FDA recommends that the sponsor periodically assess the overall RiskMAP and the tools used. The RiskMAP and tools can be changed at any time if it is felt the goals and objectives of the plan are not being met.
Communication with the FDA
The FDA is always available for consultation regarding the design and appropriateness of a RiskMAP. Within the guidance are specific recommendations for who the sponsor should contact within the FDA. Also provided within the guidance are the FDA’s suggestions regarding the content of a RiskMAP being submitted for review.
In most cases, product labeling and adverse event reporting and monitoring are sufficient for the assessment of risk. However, there are instances when more aggressive measures must be taken to establish a benefit-risk balance. Although this guidance is the FDA’s current thinking regarding the development and use of a RiskMAP, and following their suggestions is not mandatory, in my experience sponsors take a regulatory body’s “thoughts” seriously. This guidance is important in that it gives the sponsor the ability to provide a plan that will meet the FDA’s expectations. The guidance is also important in that it lets the sponsor know that the FDA will request a RiskMAP if they feel it is warranted based on their review of the safety data. Thus the sponsor is reminded that they are being watched!
For more information on this issue, contact the Kulkarni Law Firm.