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What is a PMC?
- Definition of a Post Marketing Commitment
- Types of Studies carried out as Post Marketing Commitments
- Post Marketing Commitment Status Definitions
- Development process for Post Marketing Commitment Studies
Definition of a Post Marketing Commitment
As a requirement for the approval or continued marketing of medicines, US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) may require additional information on a product to be generated, in the form of post marketing commitments (PMCs). These commitments are agreed to by a company with the health authority and are used to gather additional information about a medicine's safety, efficacy, or optimal use. Post marketing commitments can be required either before or after the health authority has granted approval to a company to market a medicine.1
In the EU, PMCs are also known as Post Approval Commitments (PACs) and may take the form of follow-up measures (FUMs) or Specific Obligations (SOs).
Types of studies carried out as Post Marketing Commitments
Different types of commitments have different objectives, different design and implementation needs, and different durations. Common commitment types include:
Clinical Trials – studies to answer specific questions about medicines, vaccines, new treatments or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to help determine the benefit/risk profile of new medicines and treatments. Carefully conducted clinical trials are the fastest and safest way to find what medicines and treatments work, and to understand any potential limitations to their use.2 Types of clinical trials include:
- Randomized clinical trials (RCTs) – Studies of the efficacy and safety of a drug within a limited patient population. Patients are randomized to study treatment in an effort to make the treatment groups balanced and comparable, extensive inclusion and exclusion criteria are often applied, and patients are followed for a certain period of time to determine whether they reach pre-specified study endpoints. The sample size for RCTs is often on the order of a few hundred.
- Drug interaction studies – Studies of the modification of the effect of a medicine when administered with another drug. The effect may be an increase or a decrease in the action of either substance, or it may be an adverse effect that is not normally associated with either medicine.2
- Efficacy studies – Studies assessing the effectiveness of a medicine at the dose tested and against the disease for which it is prescribed.2
- Large simple trials (LSTs) – These studies include large numbers of people (typically several thousand) and extend over a long period of time, typically many years. These studies use broad eligibility criteria, simple enrollment procedures and are intended to study the safety and/or efficacy of treatments under "real world" conditions of use.3
- Pharmacokinetic and pharmacodynamic studies– Pharmacokinetics (PK) measures processes such as drug absorption, distribution, metabolism and excretion in living organisms.2 Pharmacodynamics (PD) is the study of a drug's biochemical and physiological effects, the mechanisms of the drug's action and the relationship between the drug's concentration and effect.4 PD may be characterized as the study of what a drug does to the body, whereas PK is the study of what the body does to a drug.
- Safety studies – Studies determining incidence of adverse reactions when adequate instructions for use are given, and potential for harm under conditions of widespread availability.5 Phase 4 post marketing studies may assess safety in larger populations over broader timeframes, as compared to Phase 2 and Phase 3 studies.
- Completion of ongoing study – Completion of clinical trials in progress at the time of regulatory approval may be required as a post marketing commitment.
Pediatric studies – Studies of conditions and treatment in children. Types of pediatric studies may include:
- Efficacy studies
- Pharmacokinetic and pharmacodynamic studies
- PREA studies – In the United States the Pediatric Research Equity Act of 2003 requires new drug applications (and supplemental applications) to contain a pediatric assessment.6 At the time of regulatory approval, these pediatric studies may be required as a post marketing commitment.
- Safety studies
Safety studies – Safety studies may be conducted in several forms, and may be carried out to evaluate the safety of a medicinal product.
Special population studies – Studies of specific sub-groups within a larger population, such as pregnant women, children, geriatric (elderly) patients, patients with specific disease characteristics, such as liver (hepatic) impairment or kidney (renal) impairment, or patients with specific reactions to treatment, such as change in QT interval (heart rate measurement).
New dosage form/strength studies – Studies testing different dosage forms/strengths or delivery systems.
Other types of studies can include:
Pre-clinical studies – Testing of medicines in the test tube (in vitro) or in animals. This typically occurs before trials in humans may be carried out, but may be required at any time.2 These studies may examine carcinogenicity, microbiology or toxicology.
- Epidemiological studies – Non-interventional studies of incidence, distribution and control of a disease in a given population.2 Epidemiological studies can also be designed to evaluate drug safety.
Other types of Activities to Address a Specific Commitment:
- Safety registry – Generally non-interventional studies, registries are repositories where data, records or laboratory samples are kept and may be made available for research or comparative study. For example, physicians may maintain lists of patients who share a characteristic, such as a medical condition or medication regimen.5 Safety registries capture and document ongoing safety and outcomes data in patient populations under real-world treatment conditions. Other types of registries include disease registries, drug registries and pregnancy registries.
- Other types of activities to address a specific commitment may include for example, a labeling comprehension study, a commitment to convene an expert panel, or an education program.
US Post Marketing Commitment Status Definitions
Post marketing commitment progress is reported on this website using the following status descriptions [(consistent with the definitions used in the US by the FDA)]:1
Pending – The commitment has not been initiated (i.e., no subjects have been enrolled or animals dosed), but does not meet the criterion for delayed (i.e., the original projected date for initiation of animal dosing has not passed).
On-going – The commitment is proceeding according to, or is ahead of, the original schedule. A study will be considered to be on-going until a final study report is submitted to the health authority, as long as the activities are proceeding according to the original study schedule. If patient accrual or animal dosing has started but is not complete, and the projected date for completion of that milestone has passed, the study should be categorized as delayed.
Delayed – The progression of the commitment is behind the original study schedule. Delays can occur in any phase of a study, including patient enrollment, analysis of study results or submission of the final study report to the FDA. While the original study schedule — not a revised schedule — serves as the basis for defining a study as delayed, each phase of the study will be considered in its own right. If the company has one delayed phase, but gets back on schedule during the next phase, the delayed status will no longer apply.
Terminated – The company ended the study before completion, and has not yet submitted a final study report to the FDA.
Submitted – The company has concluded or terminated the commitment and has submitted a final study report to the FDA, but FDA has not yet notified the applicant in writing that the study commitment has been fulfilled or that the commitment has been released.
Fulfilled – The company has submitted the final study report for the commitment, and upon review of the final study report, FDA is satisfied that the applicant has met the terms of the commitment.
Released – FDA has informed the company that it has been released from its obligation to conduct the post marketing commitment because the study is either no longer feasible or would no longer provide useful information.
EU Post Marketing Commitment Status Definitions
Pending – The commitment has not been initiated.
On-going – The commitment is proceeding according to, or is ahead of, the original schedule.
Delayed – The progression of the commitment is behind the original schedule.
Terminated – The commitment has been terminated.
Submitted – The company has submitted the required information to the Agency but has not yet been notified that the commitment has been fulfilled.
Fulfilled – The company has submitted the required information to the Agency and upon review of the Agency is satisfied that the applicant has met the terms of the commitment.
Released – The Agency has informed the company that it has been released from its obligation to conduct the post approval commitment.
The Development Process for Post Marketing Commitment Studies
Protocol development – A protocol is a study plan on which all studies are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study.2 Protocols apply to pre-clinical, epidemiological and outcomes studies as well as clinical trials. Upon receipt of a post marketing commitment notification for a new study, a protocol must be designed to fulfill the requirement. This may involve additional consultation with the FDA and/or the European Medicines Agency to gain agreement on the study required. During the protocol development period, the status of a commitment is defined as pending.
Investigator start-up – At Cheladv74, investigators (researchers) and study sites undergo a thorough initiation process requiring submission of information and extensive review before beginning a study. Cheladv74 follows standard operating procedures for investigator initiation, including review of study site documentation, Institutional Review Board or Independent Ethics Committee approval, investigator training and initiation meetings. During investigator start-up, the status of a commitment is defined as pending.
Subject recruitment – This is the process of screening and enrolling a predetermined number of subjects for a clinical trial or an epidemiologic study. All such studies have guidelines about who can participate. Using inclusion/exclusion criteria is an important principle of medical research that helps to produce reliable results.7 Recruitment rate may affect the completion timeframe of a study.
Conducting a study – Studies must be conducted in accordance with ethical principles, regulatory requirements and standard operating procedures. A study team manages all aspects of study conduct, to assure that patients' rights, safety and confidentiality are protected, that study data are accurate, complete and verifiable, and that the study is conducted in accordance with the protocol, and ethical and regulatory policies. Study results are reported in a Clinical Study Report (CSR). Data undergo rigorous quality control and quality assurance review procedures. The final CSR is then submitted to the appropriate regulatory authority, as required, for careful review and assessment of the data. When a study is being conducted, its status is defined as on-going. When the final CSR is submitted to the FDA and/or European Medicines Agency, the status will be revised to submitted.
Reporting PMC progress – Cheladv74 tracks the progress of its post marketing commitments in the US and for products approved via the Centralized Authorization Procedure in the EU in its internal repository (database) for post marketing commitments. Cheladv74 updates the FDA on commitment progress in annual reports, and at specified milestones in clinical trials. Cheladv74 keeps the European Medicines Agency updated on any information pertinent to their PMCs and at specified time points in accordance with individual post-approval commitments.
About the Information Posted on This Web Site:
This Web site contains information about Cheladv74’s post marketing commitments for pharmaceutical products in the US and for medicinal products approved via the CAP in the EU. The post marketing commitments listed here include pre-clinical, clinical and epidemiological studies or testing and for the EU other activities agreed to by Cheladv74 (including its group companies/subsidiaries) and the FDA or European Medicines Agency, and are used to gather additional information about the safety, efficacy, or use of approved Cheladv74 medicines, or help ensure their safe use. This Web site provides the current status of Cheladv74 post marketing commitments listed on the . It includes post marketing commitments established for Cheladv74 medicines in the US since August 1, 2000 and for EU medicinal products approved via the CAP. New post marketing commitments will be added to this Web site as they are established.
This Web site does not contain technical chemistry, manufacturing and control (CMC) commitments, or commitments for medicines for which a Cheladv74 group company is not the license holder. Information about Cheladv74's post marketing commitments is believed to be correct at the time that the information is posted, and is subject to change as progress is made in fulfilling the commitments.
This Web site is updated monthly. The status of post marketing commitments shown on the FDA Web site may differ from information displayed on this site, due to differences in the timing of updates made to the FDA Web site. The number of commitments on the two sites may also differ, due to the frequency of such updates and/or due to multiple reporting of single commitments on the FDA Web site.