post-market surveillance Archives - pepgra

Output Of The Post Market Surveillance (PMS) Plan

pepgra — Tue, 03 Mar 2020 11:52:29 +0000

In Brief

The new European Union (EU) post-market surveillance (PMS) plan would act as a detailed tool for benefit-risk evaluation for medical devices.
If the PMS is appropriately structured and executed, the EU-PMS plan would act as an intrinsic player in setting up a novel framework for proactive safety evaluation of medical drugs and devices.

The Need for PMS

Post Marketing Surveillance (PMS) can be defined as the process of identifying and gathering information pertaining to medications or medical devices after it has been approved by the concerned authorities such as the Food and Drug Administration (FDA) in the US. With regards to medications, a systematic PMS process commenced way back in the early 1970s and since then, there has been a substantial increase in PMS. Drug and medical device monitoring following the process of approval has become mandatory for several reasons (FDA, 2020).

Way back in the past during the 1950s and 60s, the number of drugs in the market were very scant compared to today which made monitoring a rather easy process. In the present day, drug manufacturing has assumed magnanimous proportions and is being consumed at a very high rate. Several other factors that warrant the need for PMS pertains to the modifications in the approval process of the FDA.

Though the process of approval has weathered harsh criticism, the FDA has countered the criticism by setting up opportunities and mediums for patients who are in need of critical drugs (Onakpoya et al., 2016). As an outcome, it might not be possible to identify the risks (during the premarketing stage) involved in using certain drugs.

Post market surveillance is executed by several different organization types, as well as agencies. These would comprise of universities, private organizations, pharmaceutical manufacturers and consumer advocacy groups. The objective of carrying out a PMS might vary from case-to-case and on the basis of the viewpoint of the personnel who would be responsible to execute the surveillance (Pane et al., 2019). Recent instances in terms of safety issues within public health that revolved around medical devices have also accorded much emphasis on the necessity to enhance the European Union medical device regulation (EU-MDR). This was particularly in response to the public health concern that arose in 2012 from hip implants.

Total metal-on-metal hip replacements were carried out effectively amongst several patients. However, abrasions from metal-on-metal led to leaching and erosion of metallic particles into soft tissue (FDA, 2013). Thus, the metallic debris resulted in weakened bone and tissue around the implant and eventually caused the implant to fail and necessitated the need for further surgeries. In the same year, another instance that led to a scandal pertained to the poly implant prothese (PIP) breast implants. Women in excess of 400,000 received these PIP breast implants which were manufactured using silicone gel of industrial grade. This industrial grade gel was prone to rupture and caused irritation and inflammation (New york daily News, 2012). This further advocated the need for PMS.

PMS: What it involves

Considering that the process of drug approval comprises of phase I, II and III trials, post marketing trials are often referred to as phase IV trials. PMS comprises of a systematic monitoring of drugs and medical devices as they are utilized in actual real-world scenarios. This is in contrast to controlled clinical settings during pre-marketing Clinical trials wherein the conditions of the study are strictly controlled (David & Kim, 2019). Though randomized clinical trials (RCTs) that have the propensity to lower variability are beneficial in evaluating the effectiveness of one drug or device as compared to the other, they seldom provide appropriate information on the effects of the drug or device following its release in the market for use by patients.

PMS: What it offers

PMS offers information which is highly valuable with regards to utilizing drugs within special population of patients. The information that is provided would not be easily accessible from pre-marketing studies. Studies that involve an RCT that have been executed prior to marketing comprise exclusively of subjects who match the preset exclusion and inclusion criterion, thereby creating a population that is largely homogenous (Suvarna, 2010). The population that makes up potential users following the drug or device being released in the market is very different from the population that has been evaluated during the phase of pre-marketing.

For instance, RCTs generally do not include women participants who are lactating or those who are pregnant. Therefore, PMS is only the medium of acquiring information on teratogenic and mutagenic impact of drugs amongst humans (Jain & Rahul Chauhan, 2019). Other populations who stand to gain from PMS would comprise of patients having multiple comorbidities and the elderly. Akin to pregnant and lactating women, extremely old patients are also not included during pre-marketing trials. A drug might affect different populations in a different manner. For example, a 30 year old healthy patient might show a different effect as compared to an 85 year old adult with multiple health issues.

PMS Plan Outputs

EU-MDR, there is a need to have a specific PMS plan for every product within an organization’s product portfolio. All medical devices of all classes are expected to have a PMS plan whose scope would vary as per the complexity of the product and the risks it brings. The outcome of the activities pertaining to PMS would make an impact on the process of PMS during the lifecycle management of the device. Certain information derived from the PMS plan would be utilized to update other documents pertaining to PMS. An approach which is modular in order to structure the PMS plan contents would be highly beneficial in providing consistent updates to other information related to PMS.

The outputs from the PMS plan would result or impact diverse post-market documents. For instance, following a review of national registries (an aspect of the Post Marketing Clinical Follow-up [PMCF] plan), it is possible that a manufacturer might recognize a new issue in terms of safety with the product which might impact diverse post market documents; update to clinical evaluation report (CER), development of corrective and preventive actions (CAPAs), new training for users or submitting field safety corrective action (FSCA) (Pane et al., 2019).

References

1. David, S. & Kim, P.Y. (2019). Drug Trials. In: StatPearls [Internet]. [Online]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546595/.

1. FDA (2013). Metal-on-Metal Hip Implants. [Online]. 2013. Available from: https://www.fda.gov/medical-devices/implants-and-prosthetics/metal-metal-hip-implants.

1. FDA (2020). Postmarketing Surveillance Programs. [Online]. 2020. Available from: https://www.fda.gov/drugs/surveillance/postmarketing-surveillance-programs.

1. Jain, P. & Rahul Chauhan (2019). India’s New Drugs and Clinical Trials Rules: An Industry Perspective. [Online]. Available from: https://www.raps.org/news-and-articles/news-articles/2019/7/indias-new-drugs-and-clinical-trials-rules-an-in.

1. New york daily News (2012). EU to tighten medical controls after PIP breast implant scandal. [Online]. Available from: https://www.nydailynews.com/life-style/health/eu-tighten-medical-controls-pip-breast-implant-scandal-article-1.1169444.

1. Onakpoya, I.J., Heneghan, C.J. & Aronson, J.K. (2016). Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Medicine. [Online]. 14 (1). pp. 10. Available from: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0553-2.

1. Pane, J., Francisca, R.D.C., Verhamme, K.M.C., Orozco, M., Viroux, H., Rebollo, I. & Sturkenboom, M.C.J.M. (2019). EU postmarket surveillance plans for medical devices. Pharmacoepidemiology and Drug Safety. [Online]. 28 (9). pp. 1155–1165. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/pds.4859.

Suvarna, V. (2010). Phase IV of Drug Development. Perspectives in clinical research. [Online]. 1 (2). pp. 57–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21829783.

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Medical Literature Monitoring and Entering Negative Reaction Reports

pepgra — Fri, 27 Mar 2020 12:14:21 +0000

In Brief

A novel process where European Medical Agency offers a new service.
The service is focused around medical literature monitoring.
This service is also a vital step to ensure that there is no duplication of negative reaction reports.
This service came into effect from 1st September, 2015.

Service Insights

The European Medicines Agency (EMA) on 12^th May, 2015 presented an official intimation of medical literature monitoring service and also proclaimed that adverse reaction reports would be not be required to be entered within the EudraVigilance. The entire thing came into effect from 1^st September, 2015 onwards. Following the announcement, the EMA has published a list of active substances and also provided a reference to the journals that will encompass this novel service. Initially, the service was poised to be initiated by taking around a restricted number (50 active molecules) of active substances from 1^st July, 2015 and was supposed to be full-fledgedly implemented by September, 2015. As per the EMA, a preset array of journals and reference databases would be utilized for this service (Joshi, 2015). These journals / databases would include:-

EMBASE
EBSCO which would encompass a range of resources, wherein the primary focus would rest on the usage of;
- Medline Plus
- International Pharmaceutical Abstracts (IPA)
- The Allied and the Complementary Medicine Database (AMED)

To say the least, medical literature could prove to be a highly significant source for information pertaining to suspected adverse reactions from medicinal drugs. It is being offered as a service to an industry sector that for active substances and literature covered through activities of the EMA, would no more be obligated to record information related to suspected negative reactions within EudraVigilance. Any independent instances of negative drug reactions that would be found within the literature would be openly made available to marketing authorization holders (MAH). This would enable them to add the same within their safety databases and adhere to the reporting requirements beyond the European Economic Area.

PMS: What it involves

Avoiding Duplication

No doubt, medical as well as scientific literature is supposed to be a major source that offers information in terms of recognizing any suspected incidence of negative drug reactions for drugs that had been authorized in the European Economic Area (EEA).

In due accordance with guidance as outlined within the ‘Good Pharmacovigilance Practices (GVP) Module VI’, organizations that have been authorized for marketing are supposed to monitor medical literature. They were also expected to notify about individual instances of alleged negative reactions from medicines for which they held marketing authorization within the EEA. However, the outcome of such an action was that it resulted in efforts being duplicated by marketing authorization holders. The duplication was in terms of active substances that could be found in more than one medicine, as well as duplicate entries regarding such reports were made into EudraVigilance and national safety databases (Heads of Medicine Agencies, 2012).

Expected Outcomes

The European Medical Agency executes the task of monitoring medical literature and entering pertinent information into EudraVigilance with a view to;-

Improve the overall efficiency in terms of reporting negative reactions.
Present the pharmaceutical sector with a simplification.
Enhance the overall quality of data by lowering the scope for duplication.
Undertake efforts to ensure savings in resource for the pharmaceutical industry.

Extend support in terms of activities pertaining to signal detection by holders of marketing authorization and national competent authorities.

Legal Antecedents

Article 27 of Regulation (EC) No 726/2004 forms the background for the tasks of the EMA. As per regulations, it has been stated that;

Selected medical literature will be monitored by the Agency for reports pertaining to suspected negative reactions to medicinal products that are inclusive of some specific active ingredients. The Agency will also publish the list of active substances that are presently being monitored and the relevant medical literature that falls under their purview.
Pertinent information derived from the chosen medical literature will be entered into the EudraVigilance database by the Agency.
An in-depth guide will be created by the Agency following due discussions with Member States, Commission and concerned parties, with regards to monitoring medical and scientific literature and entering the required information into the database of EudraVigilance.

In tandem with Article 107, paragraph 3 of Directive 2001/83/EC, it won’t be necessary for marketing authorization holders to report suspected negative reactions to EudraVigilance that have been mentioned in the listed medical literature as monitored by the EMA. This is particularly for products that comprise of active substances that find mention within the list of substances that are under scrutiny by the EMA.

At the same time, it is also imperative to keep in mind that marketing authorization holders would still be responsible to keep a track on every other medical literature and report any suspected negative reactions (European Medicines Agency, 2020).

Active Substances Included

An extensive array of active substances which also comprises of herbals, have been chosen on the basis of the medicinal product information that has been provided to the EMA in tandem with Article 57(2), in the second paragraph of Regulation (EC) No 726/2004. Mainly a large number of active substances that are known to exist in medicines and those for which a large number of marketing authorizations which were provided to diverse marketing authorization holders within the EEA fell under this service (European Medicines Agency, 2020).

The detailed list, largely of chemicals and substance groups which were herbal and subject to being monitored by the Agency is available in a separate document on the Agency website.

Advantage Marketing Authorization Holders

The introduction of this new service by the EMA is bound to make a humungous positive impact mainly on marketing authorization holders who exist and operate in the EEA. As per estimates, around more than 3,500 marketing authorization holders for substance groups stand to gain from this service. In addition, marketing authorization holders in excess of 640 under the herbal substance group would also stand to gain an advantage through this move by the EMA (Joshi, 2015; European Medicines Agency, 2020).

References

European Medicines Agency (2020). Monitoring of medical literature and entry of adverse reaction reports into EudraVigilance. [Online]. 2020. European Medicines Agency. Available from: https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/monitoring-medical-literature-entry-adverse-reaction-reports-eudravigilance. [Accessed: 23 March 2020].
Heads of Medicine Agencies (2012). Guideline on good pharmacovigilance practices (GVP). [Online]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-good-pharmacovigilance-practices-module-vi-management-reporting-adverse-reactions_en.pdf.
Joshi, P. (2015). EMA Launches Medical Literature Monitoring Services: To improve the safety monitoring of medicines by enhancing the quality and consistency of data. [Online]. 2015. Safety & Risk Management Blog. Available from: https://www.sciformix.com/safety-risk-management-blog/ema-launches-medical-literature-monitoring-services/.

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