Blog Archives - pepgra

Relevant Medical Databases And Search Engines For Periodic Literature Screening

pepgra — Thu, 28 Nov 2019 07:24:24 +0000

Are you looking to collect evidence for your medical writing projects? If the answer is YES, then you should always bank upon the most recent and trustworthy sources.

A medical literature search engine is a centralized browser-based platform which will come up with literature related to any of the medical subjects you choose. This is perhaps not a good idea to seek help of every medical resources discussed in this blog, yet using a few of the medical literature search engines will definitely serve the purpose of your constant source of authentic evidence.

How To Find A Medical Journal Search Engine

Search engines are programmed to be connected with the archives of published literature that are stored inside online subject-specific academic databases like the medical literature database

These huge databases of medical articles are indexed with millions of journals from all over the world. A single database cannot provide all the medical literature.

Here is a small list of databases that are used by some of the most popular medical search engines:

EMBASE:owned by Elsevier with more than 29 million records
MEDLINE: Over 22 million biomedical published papers can be found in this library
PsycINFO: more than 3.5 million collections available

Cochrane Database of Systematic Reviews (CDSR)

MedlinePlus: It is theNational Institutes of Health’s Web site Produced by the National Library of Medicine US
INDMED: National Database of Indian Medical Journals
LILACS: an on-line bibliographic database in medicine and health sciences, maintained by the Latin American and Caribbean Center on Health Sciences Information
Australian Medical Index: a database that indexes and abstracts articles from over 160 Australian health and medical journals
CBM: Chinese biomedical literature database

Below Is A List Of A Few Dedicated Search Engines For Your Medical Writing

1. PubMed

PubMed is perhaps the first web-based free search engine that can strike in the minds of the medical authors. It is a free online collection of medical journal papers collected by the National Library of Medicine(NLM) of the United States National Institutes of Health.

This includes more than 25 million documents and scans a large number of databases including the so called MEDLINE and other NLM journals like MedlinePlus.

You can filter your search with ease for each and every topic in PubMed by typing search terms to the MeSH (Medical subject text heading).This is a filtering mechanism for finding specific journal papers. It also provides PMC citation and NCBI Bookshelf.

2. Ovid

There are other search engines that seek out MEDLINE like Ovid, ProQuest ,and Ebscohost. But for this, you have to manage the login access from your university.

Ovid is a search engine that is analogous to PubMed. But It has a clear edge over PubMed as Ovid can search for more number of databases including MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews (CDSR). This depicts the fact that with Ovid, you can conduct a wider spectrum of search which will naturally provide more results and therefore more evidence for your health writing.

3. Web of Science

Web of Science holds a huge database of Thomson Reuters’s 8,700 international scientific journals. A large number of international publications are included from Asia in this archive but need a subscription to access the papers.

Web of Science is a valuable database for searching scholarly journals on the upcoming trends especially if you are writing on guidelines or protocols. It encompasses more than 250 fields in science, arts, humanities, and social science.

Web of Science Core Collection is very consistent with its content selection and ensures high-quality journals. It provides indexes that cover the content thoroughly with a complete view including citation.

4. Science Direct

Have you heard about ScienceDirect? You probably have. It is a full-text scientific respiratory, proved to be of immense help to the millions of medical writers with detailed knowledge not limiting only to the abstract.

This search engine will allow you to find articles owned by academic publisher Elsevier in over 3,800 science, technology and medicine papers.

SpringerLink is another portal similar to Science Direct. This search engine has access to more than 5 million articles in journals operated by publisher Springer.

5. Scopus

An American researcher wrote a review in 2006 indicating that if you use Web of Science frequently to search for papers, Scopus can be a great complement as neither of these two search engines look for articles that are all published

Scopus is a hefty database of more than 60 million peer-reviewed literature and is also owned by Elsevier. Scopus ties up with EMBASE and MEDLINE databases to search collections for journal articles. More than 4200 full-text journals that the search engine is connected with, will give you access to full-text articles but some of these may need login via subscription.

6. Cochrane Library

You can check the Cochrane Library if you’re searching for systematic reviews or meta-analyses. This will not only give you the results from the Cochrane Database of Systematic Reviews (CDSR), but also the control trials in MEDLINE and EMBASE, Cochrane protocols and editorials.

Cochrane library can be accessed only through subscription. However, many open-access editorials may also be retrieved, based on the timing of publishing of those articles.

7. Google Scholar

Google Scholar is a free engine indexing medical journal articles from a diversified set of databases. If you are a regular user of Google search engine then you must be familiar with Google Scholar and you can navigate and filter the results without a problem to suit your quest.

If Google search engine initially fails you with the kind of articles you are looking for, then you should try Google Scholar as it won’t disappoint you.

Open-access search engines

If your institute does not permit you to access full-text journals then it should not be a worrying factor for you as there are several health related article search engines that will provide open-access to free journal articles:

Directory of Open Acces Journals – the database has nearly 10,000 open-access journals
Open Science Directory – about 13,000 open-access scientific journals available
Free Medical Journals – indexes about 4832 peer-reviewed open-access journals
OpenMD.com – multi-source information search engine and state repository
Trip Database – a medical search engine where one can filter searches based on the type of evidence.

Summary

So if you are going to write a medical research paper or article you will get all the required information from the above-mentioned search engines and databases.

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New Medical Device Regulation: Implications for Medical Device Manufacturers

pepgra — Tue, 17 Dec 2019 10:51:31 +0000

1.0 Background

The implementation of the new medical device regulations (MDR) on 25^th May, 2017 has presented medical device manufacturers with several drastic changes in the decades old regulatory framework of the European Union (EU). The new MDR has effectively replaced the previous medical device directive (93/42/EEC) of the EU and also the directives relating to active implantable medical devices (90/385/EEC).

The new MDR offered medical device manufacturers with already approved devices in the market with a compliance time of three years till 26^th May, 2020, which is just around the corner. For certain medical device manufacturers, the new MDR offered extra time following the date of application which enables them to provide new products to the medical device market for a maximum extended time of four years. However, in this case, extra requirements would be applicable for this additional period of transition.

2.0 Objective of the New MDR

The new MDR has been passed with certain specific objectives in mind. The key objective here is to make a two dimensional impact in enhancing the safety of medical devices(Laege Middle Styrelsen, 2019), which are;

Reinforcing the rules associated with placing new medical devices within the market.
Increasing surveillance post the device’s availability in the market.

Implications of the New MDR for Medical Device Manufacturers

The new MDR warrants the need for conclusive and hard evidence that is based on data for existing as well as new medical devices(Lehmann, 2019). It has several implications and would essentially mean that medical device manufacturers have to;

Setup systems for managing quality and risk.
Consistently gather clinical evidence for their devices following its market release, to validate the effectiveness as well as safety of the device.
Provide data reports on a new centralized electronic system which will be easily available to the public.
Be responsible for determining devices that requires reclassification and those that require additional review by a notified body.
Setup systems that encompass their financial obligations in the event of unwarranted harm that arises from a defective device.

With the new MDR in force, the objective is to reinforce the rules associated with clinical investigation of medical devices, with a view to improve the availability of valid clinical information. Manufacturers are expected to adhere to stringent regulations with regards to performance, quality and safety of medical devices that they provide.

3.0 Challenges for Medical Device Manufacturers

Under the new MDR, medical device manufacturers are expected to affect substantial alterations in terms of quality assurance, product development and data reporting. Enforcement of the new MDR would mean higher cost implications and extended time required for new product development. Further, the process of clinical monitoring and gathering evidence for recertification of existing products could also prove to be an expensive proposition. Having said that, there are four key challenges(Anastasi & Hill, 2019) that the new MDR poses for medical device manufacturers and these would include;

3.1 Reclassification

As per the new MDR, major modifications will be effected to the classification of medical devices. In this case, requirements would be largely evaluated based on risk it presents to patients. For instance, specific devices that will be used on spinal cord will move up the order from class II to class III. As a process, reclassification of devices will have to undergo expensive process of certification for new products and also recertifying products that are already in the market. The focus of the new MDR would shift from approval of product to its whole lifecycle, warranting higher clinical assessment prior to approval. This would no doubt substantially slow down the production of medical devices.

3.2 High Clinical Testing Needs

Another key challenge that manufacturers are confronted with pertains to the increase in requirements for clinical testing. Owing to reclassification, manufacturers in the past who were not required to execute clinical testing, now need to be able to do so. New regulations also necessitate a reevaluation of clinical data pertaining to devices that already exist in the market. In the event that the data does not match the new requirements, medical devices need to be put through additional testing for recertification. This further augments the cost of sustaining legacy devices.

3.3 High Demand for Notified Bodies

As of now, notified bodies (NBs) acted as consultants in facilitating medical device manufacturers to adhere to the requirements for CE markings. With the enactment of the new MDR, NBs will assume the role of enforcers who will assess all medical devices (other than IVDs), those that fall above class I. However, the shortage of NBs to evaluate devices, specifically in devices classes that are of higher risk, will lead to a delay in approval for products and slow the entry of a device into the market. Furthermore, timelines are bound to be increased considering that NBs have a huge volume of data to review. This in turn, would tend to increase costs on the whole.

3.4 Significance on Post-Market Surveillance

Under the new MDR, much stress is being laid upon post-market surveillance. This would comprise of preemptive monitoring of the performance of medical devices for yearly safety updates for devices falling in the high risk class, recertification and prompt reporting of incidents concerning device safety. This kind of intense monitoring and reporting for safety requires additional resources which would prove to be a strain for medical device manufacturers.

4.0 Compliance

The new MDR presents some disruptive changes that have far reaching implications for medical device manufacturers. With the transition period almost at end, there are several modifications that device manufacturers need to enforce to ensure success of existing and new devices. The extent and intricacy of the challenge presented by the new MDR would require device manufacturers to bring about substantial changes in domains as vast as; data reporting, product development, manufacturing procedures and quality assurance. To comply with the new MDR, device manufacturers can strategize and conduct a gap analysis to identify whether their existing devices comply with the new MDR. Excellent leadership is vital to facilitate the smooth transition to the new MDR while developing a strategy for execution that comprises of preset timelines and techniques to monitor progress with regards to compliance. Medical device manufacturers could setup a core leadership team that would include experts from quality assurance, clinical or medical affairs, R & D, regulatory affairs, manufacturing, labeling, biocompatibility, sterilization and marketing. Members of the team need to establish an active communication with NBs while setting project harmonization between product portfolios and business units(Premier Research, 2019). On the other hand, medical device manufacturers are approaching external entities (Contract Research Organizations) to acquire support and guidance to ensure compliance(Lehmann, 2019).

Anastasi, V., & Hill, K. (2019). The top four challenges under the new EU MDR and IVDR. Retrieved December 7, 2019
Laege Middle Styrelsen. (2019). New medical devices regulations. Retrieved December 7, 2019
Lehmann, J. (2019). Compliance In Focus. Retrieved December 7, 2019
remier Research. (2019). Strategic Planning for Compliance With the EU Medical Device Regulation. Retrieved December 7, 2019,

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Challenges And Solutions To Pharmacovigilance Literature Screening

pepgra — Fri, 10 Jan 2020 09:16:25 +0000

1.0 Background

Adverse drug reactions assume much significance in terms of risk associated with safety of patients and could make a major impact on costs related to health systems. Owing to its significant implications for public health and safety of patients, regulatory authorities around the world have enforced and put into practice novel legislations related to pharmacovigilance in recent times[1]. From a historical standpoint, activities related to pharmacovigilance largely hinges on undertakings for signal detection, which is executed on data assimilated from impulsive reporting systems. But since health professionals tend to under-report any adverse drug reactions, the focus of new legislations are largely on pertinence of other safety information sources. Such sources would comprise of scientific literature for tracking the benefit-risk profile of medicinal products, as well as signal detection[2]. Simply said, scientific and medical literature could prove to be a substantial source for valid information in order to monitor the risk-benefit balance and safety profile of medicinal products[3]. This is specifically in reference to detecting emerging issues in safety or new safety signals.

During recent times, regulations related to pharmacovigilance have concentrated largely on medical literature monitoring (MLM), which is a complex procedure, the scope of which continues to deepen and widen. Current regulations offer in-depth guidance on medical literature searches and review in order to facilitate reporting of individual case safety reports (ICSRs) those that have not been directly reported to the sponsor, while helping signal detection[4].

2.0 Pharmacovigilance and Literature Screening: The Link

For the uninitiated, literature screening is a key element of pharmacovigilance. Medical and scientific literature emerges as a vital information source on cases of suspected adverse drug reactions (these are also commonly termed as individual case safety reports – ICSRs). Literature screening becomes an integral aspect in pharmacovigilance as the main objective of the screening is to recognize ICSR and / or any substantially new information from studies pertaining to safety and efficacy (epidemiological, clinical and non-clinical). Such studies might not be covered through current product labeling and / or any deviation from the existing safety information pertaining to the product label, through an increase in the occurrence of aadverse reaction already known, or alteration in the specificity or severity of an event, or safety information that is inconsistent with the product label.

3.0 Challenges

The continuous growth in the number of sources for data or information, combined with the regulatory requirements could render the procedure to be a rather formidable proposition. Considering that the sources for information has increased multifold as compared to earlier, and the continuous shift in global regulations, teams functioning in the domain of pharmacovigilance are under duress to come up with strategies that are not only flexible but extensive too . Keeping in mind that screening of medical and scientific literature to pin-point adverse drug reactions are regulatory requirements for pharmaceutical organizations, pharmaceutical organizations are confronted by several challenges in terms of scientific literature screening. Considering that regulations are turning out to be more extensive and severe, and regulators too seem to have become more strict, pharmaceutical organizations are faced with the issue of amalgamating the continuously growing data on safety from literature, within their efforts towards pharmacovigilance . This is done with the objective of being compliant with regulations that are applicable. Taking into account the growth in volume on the whole and the complexities within medical literature over the course of several years, literature screening for product citations emerges to be a humungous task. This requires significant time (in excess) to be invested, cost and effort of sifting through large volumes of cross-disciplinary and heterogeneous reports. Nonetheless, there is still scope for important data to be overlooked owing to the mammoth data volumes.

4.0 Solution

The European Medicine Agency’s (EMA) latest initiative (September, 2015) is focused on lowering the number of duplicates in terms of monitoring medical literature and efforts at review by the Marketing Authorization Holders (MAHs). This initiative has the potential to enhance monitoring of drugs for safety by improving the consistency and quality of information as reported within EudraVigilance. Monitoring medical literature and entering pertinent data within EudraVigilance would be executed by the EMA in order to improve adverse drug reaction reporting efficiency, offer a process which is simple to the industry, enhance quality of data by lowering the number of duplicates, contribute to resource savings within the industry and extend support for activities pertaining to signal detection by National Competent Authorities and MAHs . This initiative is quite promising and also the first of its kind which has been launched by the EMA. Through this initiative, ICSRs found within the literature would be rendered available to MAHs, enabling them to incorporate it within their safety databases while meeting their obligations in terms of reporting .

5.0 Conclusion

In the present day, there is definitely a gnawing need for the industry to adopt novel, extensive, cost-effective and efficient solutions for medical literature screening and review with a view to match the continuously evolving marketing, regulatory and strategic requirements. At a bare minimum, to ensure regulatory compliance at an optimal level, pharmaceutical organizations should adopt enhanced tools and procedures that allow triage, monitor and review pertinent articles from every literature source available. This has to be rather rapid as well as accurate and at the same time should also have the capability to interrogate and incorporate new streams of data as they become available without any efforts being duplicated. Such solutions need to facilitate incorporation of safety data from diverse sources within a single unified repository throughout the whole lifecycle of the product, while ensuring workflow which is consistent throughout the organization.

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E-Dossier Submission: Regulatory And Procedural Guidance

pepgra — Tue, 04 Feb 2020 11:20:55 +0000

In Brief

This particular write-up presents a background about e-dossiers that are submitted to regional authorities by pharmaceutical companies for drug registrations.
The write-up highlights the pre-requisites and procedures while submitting an e-dossier.

Introduction

Right from 1990, the International Conference for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) has been consistently striving to develop a framework which is standardized with regards to drug registrations. The objective of such a standardized framework is to bring about a harmony to the maximum extent possible, the content and structure of the technical information furnished to lend support to marketing authorizations. Representatives from Japan, the European Union and the United States and from other regions that function as observers are instrumental in driving the ICH. The steering committee of the ICH during November 2000 had ratified guidelines which were established by the ICH M4 working group, elucidating the Common Technical Document (CTD) in order to register pharmaceuticals that were intended for use by humans (Bonn, 2007). This implied that the paper version of the CTD had realized Step 4 status, indicating that the ICH members had reached a consensus wherein each member was committed to integrate the ICH guidelines within the regulatory framework of each region. Culmination of this last step is termed as Step 5. Within the United States (US), the FDA has officially embraced the guidelines as laid down by the ICH as FDA guidance. Within Europe, Volume 2B of Notice of Applicants underwent modifications during 2001 to incorporate the CTD within the legislative system in Europe. From July 2003 onwards, it has been made mandatory for every applicant to submit paper dossiers in the EU, Japan and the US.

However, a growing need was felt for facilitating electronic submissions. The ICH M2 ESTRI (Electronic Standards for the Transfer of Regulatory Information) working group created the standard for electronic message exchange for CTD which was termed as the electronic common technical document (eCTD). The eCTD comes across as an electronic form of a CTD that was paper based. The eCTD specification outlines the criteria to take into account electronic submissions as technically acceptable. In addition, the standards as laid down by the eCTD outline the mediums to develop and convey an electronic submission that matches the CTD definitions (Bonn, 2007). The focus here is to offer the capability to convey the CTD from industry to a regulatory authority. Also, the eCTD considers the necessity to extend assistance over the entire lifecycle of an electronic submission or dossier. The eCTD standard founded on the initial version 3.0 specification realized Step 4 during October 2002, and is being executed across regions, escalating it to Step 5.

Therefore, the objective of this article is to outline the regulatory and procedural guidance for e-dossier submission.

Fundamentals of Electronic Submission

The specification for eCTD elucidates the format for the message and the procedure for moving submission documents and processing instructions to an agency system. Standards as laid down by the eCTD offers a medium to capture every interaction that occurs between agencies and industry, in such a way that it sheds light on modifications between multiple submissions. This lifecycle view of the submission can be realized with the help of the XML format. By using the XML format, it is possible to describe every document that is included within the submission. In addition, it also offers instructions to the system that receives the submission, thus enabling data management, which elucidates the submission. Such data is popularly known as meta data and examples of meta data at the level of submission comprises information pertaining to the submission type, the agency that will receive the submission and the applicants who submit (FAMHP, 2016). Examples pertaining to meta data at the level of document would comprise of information regarding the version, descriptive information as in name of documents and time stamps and language. On the whole, the ability of the XML to segregate content from structure holds the key in terms of its versatility and increasing popularity. It has several uses, enabling users to restyle and reformat to match diverse media types, recognize elements, reuse portions, exchange data and sustain and output several versions for the same document.

As an outcome, extra specifications have been setup by several regions on the basis of XML format for content in the eCTD standard. These are frequently replace document files that are unstructured (eg; -doc, -pdf, -rtf) with XML documents that are highly structured and exemplified by the FDA’s Study Tagging File (STF) or Europe’s electronic Application Form (eAF), in tandem with initiatives at labeling like the FDA’s structured product labeling (SPL) and EMEA’s product information management (PIM). This trend can also be viewed as a consistent extension of the eCTD standard making the submitted information largely granular and more in a position to be managed with ease by systems which are automated. This, more often augments the efficiency and quality of the process of regulatory review.

Acceptance of e-Dossiers

The NCA Medicines and Healthcare products Regulatory agency (MHRA) in the UK has been since 2005 accepting electronic submissions while the paper format has been completely stopped since 2007. As a matter of fact, MHRA has made eCTD a mandatory requirement. While Belgium has embraced eCTDs largely, they still accept other formats. The same holds true for the Netherlands, Norway, Germany, Sweden, France, Denmark, Ireland and Austria. For nations like Romania, Cyprus, Spain, Czech Republic, Finland, Iceland, Lithuania, Latvia, Poland, Bulgaria, Estonia, Greece, Italy, Slovak Republic, Hungary, Liechtenstein, Luxembourg, Malta and Slovenia, no information is available with regards to eCTD standards.

Conclusion

Application of the eCTD standard within the XML format tends to allow an applicant’s submission documents to be reused within diverse regional markets. The submission is made up with five key modules wherein the first module comprises of all documentation specific to the region. Exchange of this very initial module with a module pertaining to another agency enables a highly effective re-submission process across diverse markets, without feeling the need to modify the documentation or the meta data from the rest of the four modules. Yet another benefit is that by creatively utilizing XML meta data, it is possible to outline the table of contents in different manners, enabling an application to have views that are specific to discipline (for instance; clinical vs. chemistry), lifecycle views that are cumulative which reveals every document and its existing state, views that are specific to submission revealing only the delta amongst submissions, module specific views etc., every additional particulars encouraging assembly efficiency and reviews.

References

Bonn (2007). Electronic Submission and the MRP/DCP: How to Compile a Dossier That Will be Accepted at the European Agencies. [Online]. der Rheinischen Friedrich-Wilhelms. Available from: https://dgra.de/media/pdf/studium/masterthesis/master_benning_l.pdf.

FAMHP (2016). eSubmission Guidelines. [Online]. Available from: https://www.famhp.be/sites/default/files/downloads/eSubmission Guideline revision 2 13final30102015.pdf.

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Overview Of The Main Differences During New Product Development Between Medical Devices And Medicines

pepgra — Tue, 11 Feb 2020 07:10:36 +0000

In Brief

Medicines and devices that are supposed to be launched are based on industry composition where above 80% small and medium-sized companies require medical devices and large multinational organizations seek new medicines
One of the fundamental variations refers to the active components within medical devices (similar components are used in electrical and mechanical engineering tools). On the other hand, drug development involves knowledge of chemical, pharmacological, genetic engineering and biotechnology.

Healthcare industry has undergone various transformations every time to launch a new medical device and medicines. In order to achieve the approval, these products are subjected to few general rules to prove their efficiency through a thorough supervision and evaluation and then finally step into the biotech market (Management, 2020). Every patient struggling to overcome or manage the chronic disease survives with a hope that a day may bring better medicines that can permanently cure the disease. In a survey it was found that America’s biopharmaceutical research companies are tremendously working towards the invention of new medicine which can gradually improve patient’s health and save many patients life. However, it was estimated that since 2000, FDA has sanctioned and approved more than 500 new medicines helping patients to live longer and healthier. Many medicines are potential to cure various diseases like cancers cardiovascular disease and offering new options for patients suffering with diseases like Alzheimer’s and Parkinson’s (Pharma, 2019).

Akin to prescription of medicines, medical devices are approved and regulated by the Food and Drug Administration (FDA). However, the regulatory framework established by the Congress for the medical devices is flexible in various aspects, which could be due to the underlying differences between medical devices and prescription of the drugs (Parliament, 2017).

The FDA play a key responsible role in regulating and supervising the safety of drugs, foods, vaccine, blood products, medical devices, biological medical products, dietary supplements, radiation emitting products, cosmetics and veterinary products. Another department Within the FDA is the Center for Devices and Radiological Health (CDRH) which ensures the effectiveness of medical devices and its safe use. It also suggests to eliminate the products that emit various radiations which are hazardous to human kind (Sutton, 2011).

When a new medical device or medicine is about to launch in market it undergoes few stages that validate the product. However, there are some basic existing differences between the new medical device and new medicine which has to be launched and are based on industry composition where above 80% small and medium-sized companies require medical devices and large multinational organizations seek new medicines. In general the active components in medical devices are materials used in mechanical and electrical engineering tools, whereas, to produce a new medicine the pharmacology and chemistry composition are essential and biotechnology, genetic engineering techniques are essential. However, the pharmacologic properties and action of active ingredients in medicine is understood based on pre-clinical and clinical studies, standardised batch sizes, manufacturing processes and starting materials products that are stable and generally stored at room temperature with a long shelf life.

Figure 1 Different stages of Medical device development and drug development

Source: Mahapatra et al.,(2018)

Another important difference is product development where, medical devices are manufactured by varieties of products by the healthcare professionals, which is approved based on their specific function, safety and efficacy. On the other hand, based on trial and discovery basis medicine preparation which is usually in the form of pills, ointments, aerosols and solutions are developed by chemists and pharmacologists in the laboratories (Australia, 2020; Devices, Vitro, & Medical, 2012) . Apart from the above mentioned differences, U.S. Drug and Device Development have listed major developmental features which are crucial. The pre-market approval is essential for the high-risk medical devices which are grouped under Class III medical devices. With Class III medical devices, the rate of technology change, ease of in vitro assessment, influence of physician technique and ability to visualize performance were found to have high output than the new medicine which is usually low. A single pivotal study is enough to evaluate the efficacy of Class III medical devices, but for a new medicine two studies are required to cross check. For Class III medical devices, a variation in voltage is found through comparators and for new medicine it was concurrent control (RCT). It is difficult for Class III medical devices to show its ability to blind treatments than new drug which is easy. In order to evaluate the Class III medical devices, the study population size required is small in 100’s when found with new medicine which is large in 1000’s. Moreover, to evaluate the total product life cycle of Class III medical devices consumes months-years and for new medicine it takes years to decades.

Pertaining to pre market data use, the New Devices follows 21 CFR 860.7(c)2 quotes that “Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. The evidence required may vary according to the characteristics of the device, its conditions of use, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use.”

New Drugs follow 21 CFR 314.126, refers to sufficient reports obtained through well-controlled investigations which provided the proof of “substantial evidence” in order to provide the information on the effectiveness for the new drug. However, a sufficient and well-controlled study uses a design that permits a valid comparison with a control to provide a quantitative assessment of drug effect • Historical control designs are usually reserved for special circumstances • Uncontrolled studies or partially controlled studies are not acceptable as the sole basis for the approval of claims of effectiveness.

Common Key Regulatory Decisions for Approval: Is the drug/device safe and effective in its proposed use(s), and do the drug/device benefits outweigh the risks. What should the label contain? Is the proposed labeling (package insert) appropriate for the drug/device, are the methods used in manufacturing the drug/device and the controls used to maintain the drug’s/device’s quality adequate to preserve the identity, strength, quality, and purity of the drug or the durability, performance, sterility and biocompatibility of the device (Laschinger, 2019).

References

Australia, M. T. A. O. (2020). Difference between medical devices and pharmaceuticals. Retrieved from https://www.mtaa.org.au/devices-vs-drugs

Devices, M., Vitro, I., & Medical, D. (2012). Differences between medical devices and drugs Medical Devices In Vitro Diagnostic Medical Devices Drugs. 1–3. Retrieved from http://globalmedicaltechnologyalliance.org/papers/GMTA_Differences_Between_Devices_IVD_Drugs_RevFINAL_17July12-pdf-pdf.pdf

Laschinger J. (2019). Regulatory Pathways Devices vs. Drugs Are there roles for registries? 1–17. Retrieved from https://www.ctti-clinicaltrials.org/files/session1-2_laschinger_regulatorypathways_regtrial_march30.pdf

, I., Clark, J. R. A., Dobson, P. J., Owen, R., Lynch, I., & Lead, J. R. (2018). Expert perspectives on potential environmental risks from nanomedicines and adequacy of the current guideline on environmental risk assessment. Environmental Science: Nano, 5

Management, H. (2020). Health Management and Leadership promotion, cross-collaboration amongst key disciplines. Retrieved from https://healthmanagement.org/

Parliament, E. (2017). Medicines and Medical Devices. Retrieved from https://www.europarl.europa.eu/factsheets/en/sheet/50/medicines-and-medical-devices#_ftnref1

Pharma. (2019). Medicines in Development. Retrieved from https://www.phrma.org/en/Science/In-The-Pipeline/Medicines-in-Development

Sutton, B. (2011). Overview of Regulatory Requirements: Medical Devices – Transcript. Retrieved from https://www.fda.gov/training-and-continuing-education/cdrh-learn/overview-regulatory-requirements-medical-devices-transcript

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Preparing For The Future: The New European Union Medical Devices Regulation

pepgra — Tue, 18 Feb 2020 05:52:53 +0000

In Brief

For long, medical device regulations continued to remain stagnant till such time that the world was struck with the hip replacement and breast implant crisis.
The new EU-MDR and EU-IVDR brings in more stringent regulations, drastically modifying the way in which medical device manufacturers operate. The new regulations have also modified several device classes that were previously quite lenient into classes that now require strict review and evaluation. It also takes into its ambit accessories to medical devices that were previously unregulated.

Right from the early 1990s, there has hardly been any changes in terms of regulation of the medical device industry within Europe. Nonetheless, owing to some incidents during the recent past, comprising of the crisis revolving around hip replacements and breast implants has now incited the need for stringent compliance and regulatory reforms within the industry. The most prominent amongst all regulations were the European Commission’s 2012 proposal for regulation on medical devices (EU-MDR) and in-vitro diagnostics (EU-IVDR). With the publication of guidance in a formal manner very imminent, the proposal intends to offer national regulators with a control that is much more superior and also provide any inherent oversights within the medical devices sector, while rendering it mandatory to conform to the new regulations (Doloitte, 2016). In the event that medical device manufacturers fail to conform to the changes, it would most probably lead to the medical device manufacturer forfeiting its manufacturing license.

The impact that would be created by the new EU-MDR could bring about drastic modifications to the manner in which medical device manufacturers function. So much so, that it has the potential to make an impact on the composition of the device manufacturers current as well future portfolios. Further, conforming to the regulations would also result in substantial costs. Therefore, it becomes imperative that device manufacturers act now in order to acquire buy-in by stakeholders, ready their organizations and commence with adopting the suggested modifications.

The new EU-MDR 2017/745 brings legislation in EU at par with technical developments, modifications within medical science and advancements in terms of law-making. Implementation of the new EU-MDR would eventually establish a regulatory framework that is transparent, robust and sustainable, which will receive global recognition, thereby enhancing clinical safety and facilitates manufacturers with an access to market which is fair. In contrast to directives, it is not necessary to transpose regulations within national law. Thus the new EU-MDR would restrict any discrepancies in terms of interpretation throughout the EU market (European Commission, 2020). It can be thus said that the new EU-MDR is preparing the medical devices market for the future. However, there are aspects that medical device manufactures need to take into consideration in preparation of the future.

Preparing for the Future

The European Commission has of late published five documents with the intention of providing guidance to manufacturers as well as other economic operators with regards to the changes effected through the new EU-MDR and EU-IVDR which are due to be in-force from May, 2020 and May, 2022 onwards respectively. The said guidance related documents comprise of implementation models as well as factsheets for medical device manufacturers as well as in-vitro medical device manufacturers, along with an extensive list of requirements for medical device manufacturers (Grow, 2020). Those manufacturers who have not commence execution of the new EU-MDR can refer to these guidance documents as an initial roadmap, whereas, those manufacturers who have already progressed with the execution can refer to it as a checklist in order to ensure that they cover all steps within their plan of action.

The factsheet concentrates on key modifications as outlined by the EU-MDR and provides insights on the scope of the EU-MDR, definitions, obligations of manufacturers, class of risks for devices, notified bodies, system of identification of new devices, evaluation of adherence, along with clinical needs and a brief of clinical and safety performance. It offers vital points on the EU-MDR background, modifications executed through the new regulations and practical outcomes and the timelines for making the modifications. In addition, the guidance document also presents answers to some basic operational queries.

Furthermore, what needs to be taken into consideration is that the new EU-MDR outlines strict requirements for designating notified bodies (Grow, 2020). Also, the new EU-MDR has an extended scope and takes into its ambit more devices such as; devices for cleaning, sterilizing or disinfecting other medical devices, medical devices for single use that are reprocessed and some specific devices that have no intended medical purpose. Moreover, certain devices have also been reclassified on the basis of risk analysis while introducing a procedure of consultation on clinical evaluation. This is purportedly executed by a panel of independent experts for certain classes of devices (class IIb) and for devices falling under the implantable (class III) category (Grow, 2020).

Approach to EU-MDR Conformity

Considering the intricacy and extent linked with executing the new EU-MDR, it is imperative that manufacturers adopt a cross-functional approach which extends across the enterprise. Essentially, there would be three steps to execute and adhere to the new EU-MDR and acquiring conformity.

Acquiring and in-depth understanding of the EU-MDR and EU-IVDR (Step – 1)

It would be necessary that medical device manufacturers have an enhanced understanding of the new EU-MDR, its overall impact and scope on their business. Several manufacturers would be having an amalgamation of products therefore the proposed modifications make sense. It would also be significant to comprehend any overlap with other pertinent directives and regulations such as clinical trial regulation (CTR) for human use and IVD etc.

Review and Evaluation of Medical Device Portfolio (Step – 2)

The entire gamut of products manufactured by a manufacturer needs to be necessarily evaluated and reviewed in line with the EU-MDR and requirements of the future. For instance, as per the new regulation those products that have been categorized as accessories would fall under the ambit of medical devices. There is also scope that as per new requirements, classification status of certain products might change. It would be imperative to understand whether such products need to be up-classified in future and its corresponding impact (Doloitte, 2016).

Strategy and Roadmap for new EU-MDR (Step – 3)

Following the complete review and evaluation of the product portfolio as per the existing and future states, it would be possible to define gaps. Such gaps can be necessarily categorized as tactical and strategical projects, which can be prioritized on the basis of legal, business and regulatory drivers.

To structure a regulatory strategy for affecting the new EU-MDR, there is a need for device manufacturers to define a logical sequence of activities. This warrants the need for an approach that is multi-level and would comprise of; impact evaluation of the highest levels, planning, execution and organizational alignment, communication and realization of benefits.

Future Scope

In future, medical devices that have not been covered under EU-MDR such as products that are known to utilize viable biological components for its intended purpose should also be included under the ambit of EU-MDR and EU-IVDR.

References

Doloitte (2016). Taking charge of the new medical device regulatory environment: From complex regulation to impactful change. [Online]. 2016. Available from: https://www2.deloitte.com/content/dam/Deloitte/global/Documents/Life-Sciences-Health-Care/gx-eu-med-device-regulation.pdf.

European Commission (2020). Internal Market, Industry, Entrepreneurship and SMEs. [Online]. 2020. Available from: https://ec.europa.eu/growth/sectors/medical-devices/regulatory-framework/getting-ready-new-regulations_en.

Grow (2020). Factsheet for manufacturers of medical devices. [Online]. 2020. European Commission. Available from: https://ec.europa.eu/docsroom/documents/31201.

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Medical Device Classification In The European Union

pepgra — Mon, 02 Mar 2020 10:24:04 +0000

In Brief

Different medical devices have different parameters through which it can be classified. With that reasoning, it does not make sense to subject all medical devices to stringent conformity assessments.
Moreover, the onus of classifying a medical device is the responsibility of the medical device manufacturer. The device manufacturer has to be aware about the class under which their device will fall under, right from the time the device is in the process of development.

Philosophy of Medical Device Classification

In terms of practice it cannot be economically justified nor is it feasible to make all medical devices go through every stringent assessment in terms of conformity. A system of control which is graduated should be more than enough. Under the tenets of such a system, the degree of control matches with the degree of possible risks innate within a specific device type. This warrants the need for a system for classifying medical devices. This ensures that medical devices are applied through the required process for evaluating conformity (Wheeler, 2018). With a view to ensure that evaluation of conformity as per the European Union Medical Device Directives operates in an effective manner, it is imperative that manufacturers are in a position to determine the category under which their devices will classified right from the very initial developmental phase of the device. Thus, the need was felt to establish a system of rules for device classification as under the Directive. This would allow all device manufacturers to classify their own devices.

The system of classification of medical devices is based on risk on the basis of susceptibility of the human body while keeping in mind the potential hazards linked with the device. An approach of such kind facilitates the utilization of a preset criterion that could be amalgamated in diverse manners with a view to determine classification (Global Legal Research Center, 2014). For eg., the time period during which the device is in contact with a human body, the level of the device’s invasiveness and systemic vs. local effect. Such criterions could then be applied to an extensive array of diverse medical devices and technologies. These are commonly termed as the rules for classification and have been outlined within Annex IX of Directive 93/42/EEC. To a large degree, it matches to the rules of classification setup by the Global Harmonization Task Force (GHTF) within the guidance document GHTF/SG1/N15:20063.

Prior to a medical device being legally classified by manufacturers as ‘CE’ within Europe, it is mandatory that they adhere to the appropriate medical device directive or regulation as outlined by the European Commission (EU). It is critically very significant to be aware of the appropriate medical device classification for a particular product prior to placing a ‘CE’ mark on the device. Regulatory requirements are impacted through device classification and also the route for approval along with associated costs (French-Mowat & Burnett, 2012).

Medical Device Classification in Europe

The initial step within the regulatory process in Europe would be to determine the directive that is applicable to a particular product. A large number of devices fall under the medical device directive 93/42/EEC, however, there are certain high risk devices such as implantable devices that needs to adhere to the Active Implantable Medical Devices Directive (AIMDD) 90/385/EEC. At the same time, the In Vitro Diagnostic Directive (IVDD) 98/79/EC is applicable to In Vitro Devices (IVDs) (HPRA, 2009). In case, a manufacturer opts to project adherence to regulation, the Medical Device Regulation (MDR) No. 2017/745 (for active implantable devices or medical devices), or the In Vitro Diagnostic Device Regulation (IVDR) No.2017/746 would be taken into account. A rule based scheme of classification is utilized by Europe for medical devices which fall under the ambit of MDD. There are around 18 rules which have to be adhered to and these can be referred to in Annex IX of the MDD. Though the overall structure of the rules from MDD is maintained in the MDR, there is scope for expanding the rules (McDonough, 2019).

Segmentation of Medical Devices within Europe

On the whole, every medical devices can be segmented into four key categories. These would include;

Non-invasive medical devices
Invasive medical devices
Active medical devices
Special Rules (comprising of disinfectant, contraceptive and radiological diagnostic medical devices) or devices comprising of animal tissue or drug-device combination.

The above said 18 rules as specified within Annex IX of the Directive and pertinent regulation lay down the fundamental principles for classification. As per MEDDEV 2.4/1 Rev.8, such rules are additionally elucidated with descriptive samples. The 18 rules are further bifurcated into four groups.

Rules	Device
Rules 1-4	Non-Invasive Devices
Rules 5-8	Invasive Devices
Rules 9-12	Active Devices
Rules 13-18	Special rules e.g. devices containing tissue of animal origin, due-device combinations

Furthermore, the MDR has also framed certain special rules that also cover Nano-materials (Donnell, 2016). Medical devices are further segmented as per the classes as mentioned below. IVDs are known to have their individual scheme of classification whereas, active implantable medical devices fall under the scope of similar requirements as that of class III devices (the MDR also includes active implantable medical devices).

Class I – Provided non-sterile or devices that are devoid of a measuring feature (low risk)
Class I – Provided sterile and / or is inclusive of a measuring feature (low/medium risk); to this group reusable surgical instruments as Class I reusable surgical instruments have been added by the MDR.
Class IIa – (medium risk)
Class IIb – (medium or high risk)
Class III – (high risk)

When to apply the Health Products Regulatory Authority (HPRA) for Determining Classification

As mentioned above, it is the responsibility of the device manufacturer to determine the right class for their product. Subsequently, the basic responsibility for device classification rests on the manufacturer. The manufacturer is supposed to confirm classification with a Notified Body (NB) of their preference. In case there is uncertainty or any kind of difference of opinion between the manufacturer and the NB, it is essential to refer the issue to a competent authority for arriving at a decision (HPRA, 2009). The HPRA also accepts formal requests on the part of the manufacturer for classifying a medical device, drug-device combination and borderline product before submitting an application for CE marking to a NB or before notification pertaining to the register of Class I devices. Formal requests for classification are also accepted by the HPRA from other interested parties or individuals. All interested parties can download the relevant form ADV-F0006 for medical device classification, from ‘publications and forms’ section of the HPRA website.

References

Donnell, M.O. (2016). Nanomaterials and medical device regulations Nanomaterials. [Online]. Available from: https://www.bsigroup.com/globalassets/meddev/localfiles/en-gb/webinars/bsi-md-nanomaterials-presentation-30-nov-2016.pdf.

French-Mowat, E. & Burnett, J. (2012). How are medical devices regulated in the European Union? Journal of the Royal Society of Medicine. [Online]. 105 (1_suppl). pp. 22–28. Available from: http://journals.sagepub.com/doi/10.1258/jrsm.2012.120036.

Global Legal Research Center (2014). Approval of Medical Devices. [Online]. 6462 (September). pp. 23. Available from: www.law.gov.

HPRA (2009). Guide to Classification of a Medical Device. Health Products Regulatory Authority. [Online]. 1 (1). pp. 3–11. Available from: https://www.hpra.ie/docs/default-source/publications-forms/guidance-documents/adv-g0004-guide-to-classification-of-a-medical-device-v2.pdf?sfvrsn=10.

McDonough, C. (2019). Medical devices regulation countdown. [Online]. 2019. Available from: http://www.pharmatimes.com/web_exclusives/medical_devices_regulation_countdown_1277912.

Wheeler, M. (2018). Classification Of Medical Devices Under The Eu Mdr. [Online]. 2018. Available from: https://emmainternational.com/classification-of-medical-devices-under-the-eu-mdr/.

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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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Periodic safety update reports (PSURs)

pepgra — Sun, 19 Apr 2020 17:23:29 +0000

Introduction

PSURs are pharmacovigilance documents that provide risk-benefit balance assessment.
The notion of PSUR is to offer a wide and complex evaluation of risk-benefit balance of a medicinal product.
PSUR reporting first came into existence in 1992.
Purpose of PSUR is to provide an update of global safety experience with a specific pharmaceutical.
It is imperative to consult the guideline on good pharmacovigilance practices (GVP) while preparing PSUR.
MAHs are supposed to submit all PSURs in EU to the central PSUR repository.

PSUR; What is it?

Periodic Safety Update Reports (PSURs) are nothing but pharmacovigilance Service documents that are intended to offer an assessment with regards to the risk-benefit balance of a specific medicinal product at time points that are predetermined, following its authorization. The key idea of the PSUR is to offer an extensive and vital evaluation of the risk-benefit balance of the product, while taking into consideration novel or emerging information related to safety in the context of increasing information pertaining to benefits and risks. The European Medical Agency as well as other national competent authorities evaluate information that is contained within PSURs to understand whether there were any new risks recognized for a medicine and or / if there has been a change in its benefit balance. With the help of a PSUR evaluation, it is possible to determine whether any additional investigation for a particular issue were required, or whether an action was essential to safeguard the health of the general public (for instance; an update of the information that has been offered to patients as well as healthcare professionals.

PSUR; Origin and Recognition

The notion of PSUR reporting is said to have taken root from 1992. It has found recognition and is noted at diverse platforms. This is also inclusive of the International Conference of Harmonization (ICH) and the European Union and it has been noted that PSUR reporting has not matched pace with the due developments that have taken place in pharmacovigilance literature search like electronic adverse event reporting, and planning for risk management.During the year 2010, an awareness of such type has led to alterations in European Legislation laying down the needs for PSUR reporting. On the basis of a study conducted in the past, regarding determinants of safety associated

regulatory actions for bio-pharmaceuticals, it was found that evaluations through PSUR contributed to around 38 per cent of post-authorization regulatory actions within a sample of bio-pharmaceuticals. Furthermore, during the year 2010, it was found by that around 64 per cent of selection of adverse drug reactions (ADRs) stemmed through PSURs. The said two studies scrutinized the contribution of PSURs to recognized safety signals, that do not offer any insight into the manner in which PSURs are responsible for the purpose of safety monitoring, or the percentage of PSURs that results in regulatory action.

PSUR; Purpose

The onus of keeping track of the bio-pharmaceutical products rests on the shoulders of Marketing Authorization Holders (MAHs), once they are in receipt of authorization for marketing. It is well-known that MAHs are continuously engaged in dialogue with regulators to make sure that the appropriate strategies are deployed to optimize the advantage to risk ratio of their products. One of the key tools that are put to use to enable the post-authorization communication amongst MAHs and regulators is the PSUR. The purpose of PSUR is to offer an update of global safety experience with a particular pharmaceutical. This also includes data from safety data from observational and interventional studies, spontaneous reports along with other information pertaining to safety[1].The purpose of PSUR is also to proactively analyse, present and assess novel or altering safety related data from any source assessed with regards to estimates of product exposure, though the overall coverage of data sources would have restrictions in terms of practice.

PSUR; Preparation

The preparation of PSUR is an arduous and intricate procedure and requires much care and consideration. Keeping in mind the fact that PSURs are supposed to be prepared by MAHs, it is imperative that they mandatorily consult the ‘guideline on good pharmacovigilance practices (GVP): Module VII – PSUR’. Further, to facilitate the proper and appropriate preparation of the PSUR, the European Medical Agency has created an explanatory note to GVP module VII, that all MAHs are expected to consult at the time of preparing periodic safety update reports. The proper preparation of the PSUR will tackle particular problems in the European Union evaluation procedure for products that are nationally authorized. However, the issues could also be applicable to products that have been authorized in a central manner.

PSUR; Submission

Legal necessities for PSUR submissions had been setup through regulation (EU) No 1235/2010. Directive 2010/84/EU and in commission implementing regulation (EU) No. 520/2012. The PSUR format adheres to the structure that has been outlined in the Implementing Regulation Article 35 and module VII of the guidelines of good pharmacovigilance practices (GVP) offers guidance on the preparation, submission and evaluation of PSURs. The particular format is mandated by law for nationally authorized products (NAPs) and centrally authorized products (CAPs)[4]. Marketing Authorization Holders are supposed to submit PSURs as per the data lock points that have been duly published within the EURD list. The legislation brings in derogation for routine PSUR reporting for specific products. Till such time that there is a particular condition within the authorization, or it has been mentioned to the contrary in the EURD list, there is no need for routine PSUR reporting,particularly for medicinal products that have been authorized as per the articles of Directive 2001/83/EC.

As on 13^th June, 2016, it is necessary for MAHs for submit all PSURs within the EU to the central PSUR repository by utilizing the eSubmission gateway / web client. It is compulsory for MAHs to utilize the PSUR repository for centrally as well as nationally authorized medications, irrespective of whether it is following the single assessment of the EU or a purely national process of assessment.

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