Product & Patient Safety
Product & Patient Safety
We recognize that when people take our medicines and vaccines they must have confidence in their efficacy and safety.
Our company’s medicines and vaccines are widely tested before they are approved for marketing. This testing is governed by a comprehensive regulatory scheme and by our research policies. We assess the safety of our products in rigorous nonclinical and clinical trials before they are approved. Learn more about our clinical trials.
Our company’s chief medical officer holds overall responsibility for the benefit/risk of our pipeline and marketed products, provides medical oversight for all clinical programs, supervises the development and implementation of medical policies (including those related to data transparency and the sharing of clinical data) and has authority over the design, execution and implementation of pre-registration expanded access (“compassionate use”) programs.
Our company’s Global Safety function manages a global system for the collection, management and reporting of adverse experience (AE) reports received by our company worldwide.
Monitoring & Quality Assurance
MRL Quality Assurance (QA) provides independent assurance that we safeguard the rights and well-being of patients and the welfare of animals, deliver high-quality data, and comply with applicable regulatory requirements through sound processes and procedures.
MRL QA is responsible for monitoring and maintaining the MRL Quality Management System, assures the strength of our company’s pharmacovigilance system, assures that clinical trials and regulated research are conducted in alignment with relevant regulations and guidance, and provides monitoring over MRL’s Animal Care and Use Program.
The MRL QA Good Clinical Practice (GCP) and Good Pharmacovigilance Practice (GPVP) audit programs are comprehensive, risk-based audit and oversight programs that encompass a broad range of assessments including those listed below:
- Clinical investigator sites: Audits to assess compliance with the protocol and with relevant global and local regulations/guidance (e.g., GCP & GPVP regulations)
- Vendors: Pre-contractual assessments and selected post-contractual audits of contracted research organizations (CROs), central laboratories and other third-party business partners or service providers supporting clinical and/or post-authorization activities
- Computerized systems and technology: Audits and assessments of the relevant computerized systems and technology that support MRL
- Internal process/systems audits: Systematic evaluations of adherence to relevant internal policies, standard operating procedures and guidelines as well as applicable global and local regulations/guidance
- Country operations audits: Periodic and systematic audits of our company’s activities carried out by our subsidiaries worldwide
- Business partner audits: Audits of external companies with which a licensing or development agreement exists and where compliance with contractual and regulatory requirements is assessed
- Patient support programs and marketing research: Audits of vendors engaged in customer engagement programs that may solicit data relating to pharmacovigilance
The MRL QA GLP audit program is a global, comprehensive, risk-based audit and oversight program that is designed to meet the explicit responsibilities set forth in the Good Laboratory Practice Regulations. Additionally, quality assurance oversight is provided for internal clinical bioanalysis and vaccine clinical assay testing, assuring adherence to regulatory expectations. The scope of the audit program includes the following:
- In-lab audits: Audits of ongoing study activities ensuring adherence to study protocols, associated procedures, and regulatory expectations enhancing quality by design
- Document and data audits: Audits of study outcomes for efficacy and/or safety profiles supporting research and marketing submissions
- Vendor audits: Audits of contract research organizations conducting or supporting nonclinical studies for the purposes of assuring study, systems and facilities adherence to global regulatory requirements
The MRL QA Animal Welfare audit program is a global, comprehensive, risk-based audit and oversight program function designed to ensure that the Animal Care and Use Program at each MRL research site meets required standards and is in compliance with all applicable legal requirements covering animal research.
The scope of the audit program includes the following:
- Post-approval monitoring audits: Audits of ongoing animal research activities to ensure that research is conducted in accordance with the protocol approved by our Institutional Animal Care and Use Committee (IACUC)
- Vendor audits: Due diligence audits of contract research organizations conducting animal research studies on behalf of our company. The purpose of these audits is to ensure that vendors utilize the highest standards of humane handling, care and treatment of research animals and adhere to applicable regulatory requirements covering animal research
- Animal Care and Use Program audits: Audits of MRL research sites to ensure that the Animal Care and Use Program is in compliance with internal policies and guidelines and meets regulatory standards and requirements covering animal research
MRL QA provides evidence of monitoring and independent assurance at various levels of governance throughout our company, as well as assurance that we comply with applicable regulations, guidance and guidelines and internal company policies and procedures.
CLINICAL SAFETY & RISK MANAGEMENT
Clinical Safety and Risk Management (CSRM) leads the Risk Management & Safety teams for all products, from the beginning of Phase IIb through the end of the product life cycle. CSRM is responsible for the formation of a proactive clinical safety risk-management strategy, including the Risk Management Plan, which is a regulatory requirement in many countries for marketed drugs and vaccines.
Development of the overall risk-management strategy incorporates all available internal information (e.g., basic research data and animal and human studies with the product and/or related products) and external information (e.g., literature and public data related to the class of drugs and/or therapeutic target) that contribute to the overall risk-benefit assessment of the product. The strategy focuses on activities needed to identify, evaluate and manage potential patient-safety risks. The Risk Management & Safety teams address patient safety using product labeling, physician and patient educational programs, and other risk-minimization strategies, as appropriate. The Risk Management & Safety teams also implement strategies to determine the effectiveness of these interventions, as appropriate.
SafetyMatters Initiative: The goal of our company’s SafetyMatters Initiative is to explore and implement the appropriate use of emerging technologies and methods for the identification and evaluation of health outcomes of interest (HOIs), and to further improve post-licensure monitoring and evaluation of our marketed products. A cornerstone of SafetyMatters is the proactive development and utilization, as needed, of disease cohorts (i.e., groups of patients identified as having specific conditions of interest) based on data contained in large medical claims and electronic health-record databases licensed by our company. As of May 1, 2017, our company’s Pharmacoepidemiology and Database Research Unit has successfully created and utilized 30 SafetyMatters Disease Cohorts in 18 product-specific areas. The proactive development of these cohorts greatly facilitates our ability to effectively and promptly respond to many internal or external inquiries about the epidemiology of these diseases and their treatment.
Product label reviews: The ongoing oversight and monitoring of our product labels are a major focus of our safety efforts. Our label review teams monitor information on our products and work with our product Risk Management & Safety teams to develop or update product labeling. We communicate relevant information regularly to regulatory agencies worldwide.
Innovation in Medical Evidence Development and Surveillance (IMEDS): The IMEDS program is a public-private partnership within the Reagan-Udall Foundation for the Food and Drug Administration (FDA). The aims of IMEDS are to advance the science and tools necessary to support post-marketing evidence generation on regulated products, including safety surveillance and evaluations, and to facilitate the utilization of a robust secondary electronic health care data platform for generating better evidence on the safety and effectiveness of regulated products in post-market settings. Partners in IMEDS include the FDA, pharmaceutical companies, academia and patient organizations.
Our company supports IMEDS by providing an annual grant as a founding member to support its mission as well as through representation on the Scientific Advisory Committee of IMEDS. We continue to explore synergies and linkages between IMEDS and our own SafetyMatters Initiative to establish standards for the use of modern epidemiology data sources and analytic techniques for evaluating product safety in observational claims and electronic health-record databases.
We rigorously study our products, and work with regulators and health care professionals over many years to characterize their safety profiles. Initially, test compounds are evaluated in the laboratory. If they pass stringent laboratory tests, the compounds move into next-stage testing in animals. Only a few compounds ever make it that far. If the compound makes it through the animal-testing stage, we then begin clinical development, during which multiple studies are conducted over several years.
Clinical testing begins in Phase I in a small number of people and progresses through Phase III, during which the safety and efficacy of a medicine is rigorously evaluated. If the clinical studies are successful, we submit extensive documentation and data to regulators in a product-licensing application. Before approving a medicine or vaccine for use, regulators scrutinize these extensive data and analyses. Even after a product is approved, we continue to actively monitor the safety of our medicines and vaccines in various ways, including post-marketing studies. If we identify safety issues following a product’s approval, we work closely with the regulatory authorities to communicate promptly and appropriately with health care professionals and patients.
COMMUNICATING ABOUT PRODUCT RISKS
The information leaflets in our product packaging contain information on possible side effects and, if appropriate, how to avoid some potential problems. We include contact details on our corporate website for patients, caregivers and health professionals to report adverse experiences in the United States. Outside the United States, adverse events are reported in accordance with global and any additional local laws and practices.
Depending on label changes and their context, we may determine, in consultation with regulatory agencies, that more extensive communications are appropriate. In such cases, we work with regulatory authorities to contact health care professionals in a timely manner, so that they can communicate these findings to patients through appropriate mechanisms. Contacting health care professionals might include “Dear Doctor” letters and media releases.
Adverse Event Reporting
Global Safety manages a global system for the collection, evaluation and reporting of adverse experience (AE) reports received by our company worldwide.
REPORTING AN “ADVERSE EXPERIENCE” IN THE U.S.
To speak with one of our health care professionals about our company’s products, or to report an adverse experience with a specific product, please call our company’s National Service Center at 800-444-2080. The Center can assist you Monday through Friday from 8 a.m. to 7 p.m., Eastern Time. Adverse experiences and product-related emergencies can be reported at any time by dialing 800-444-2080.
Although regulations vary by country, most countries require drug manufacturers to promptly review AE information they receive from any source, domestic or foreign, relating to the use of their products. Manufacturers are also required to have written procedures in place for evaluating and reporting adverse experiences.
In accordance with global regulatory reporting requirements, we have developed a written procedure to provide personnel worldwide (including all contractors) with a consistent and thorough process for identifying, evaluating and reporting AEs occurring in association with the use of our products. Additional detail is provided in procedures covering the reporting of AEs originating in clinical studies and those associated with the use of marketed products. Adherence to these procedures ensures timely and accurate monitoring of the safety profile of our investigational and marketed products globally.
In addition to the submission of individual AE reports to regulatory authorities in accordance with global and local timelines, we also produce aggregate safety reports quarterly, twice a year, or annually as required, for as long as we develop and market a product, for submission to regulatory authorities.
Our Risk Management & Safety teams review adverse experience information received from all sources (foreign or domestic, clinical trials or published literature, or post-marketing) for our products and determine what actions may need to be taken with reference to the evolving safety profile of our products. These teams include physicians and epidemiologists who are trained to review this type of data.
It can be difficult to determine the exact cause of an adverse experience because many patients have more than one condition and may be taking multiple products. Our Global Safety staff takes great care to make sure that AE reporting is as accurate as possible. We review the data to determine if there are any patterns or emerging trends that need additional surveillance or action.
Employees responsible for monitoring and reporting adverse experiences undergo rigorous training. New employees within our research laboratories (including all contract personnel) working in areas related to clinical research and global safety undergo training on our AE policies and procedures when they join the company. All other employees are trained in AE reporting procedures as part of our Code of Conduct training.