Pharmacovigilance

Pharmacovigilance

1. Pharmacovigilance - MHRA K. Vignesh, M.S. (Pharm)

2. adverse drug reactions - Classification All medicines can cause reactions for a medicine to be considered safe, its expected benefits should be greater than any associated risks of harmful reactions. Type A (augmented) reactions - result from usual therapeutic dose and are normally dose-dependent & also include those that are not directly related to the desired pharmacological action of the drug. Type B (bizarre) reactions - not expected from the known pharmacological actions of the drug. Type C (continuing) reactions - persist for a relatively long time Type D (delayed) reactions - become apparent some time after the use of a medicine. Type E (end-of-use) reactions - are associated with the withdrawal of a medicine.

3. Pharmacovigilance (PV) Information on safety and efficacy for a medicine before marketing is limited. The conditions under which patients and medicines are studied in clinical trials do not necessarily reflect the way the medicines are used in hospitals or general practice once they are marketed. Some adverse drug reactions (ADRs) may not be seen until a very large number of people have received the medicine, there comes a role of PV. The safety of all medicines that are monitored throughout their marketed life is known as pharmacovigilance.

4. Pharmacovigilance involves: • Monitoring the use of medicines in everyday practice to identify previously unrecognized adverse effects or changes in the patterns of adverse effects • Assessing the risks and benefits of medicines in order to determine what action, if any, is necessary to improve their safe use • Providing information to healthcare professionals and patients to optimise safe and effective use of medicines • Monitoring the impact of any action taken

5. Specific areas of interest for reporting suspected adverse drug reactions Children  Patients that are over 65 Biological medicines (such as blood products, antibodies and advanced therapies such as gene and tissue therapy) and vaccines Rare or delayed drug effects Drug interactions Congenital anomalies Herbal remedies

6. MHRA Medicines and Healthcare products Regulatory Agency (MHRA) - protect and promote public health and patient safety, by ensuring that medicines and medical devices meet appropriate standards of safety, quality and efficacy. Healthcare professionals should be able to discuss ADR/Side effects information with patients, parents and carers , be vigilant in the detection of suspected ADRs and prompt in reporting them via the Yellow Card Scheme. Yellow Card Scheme is the UK system for collecting and monitoring information on suspected safety concerns or incidents involving medicines and medical devices Purpose of the Scheme is to provide an early warning that the safety of a product may require further investigation Reports can be made for all medicines including vaccines, blood factors and immunoglobulins, herbal medicines and homeopathic remedies, and all medical devices available on the UK market he MHRA assesses the balance of risks and benefits of all medicines at the time of initial licensing and throughout their use in clinical practice and seeks advice from the independent Commission on Human Medicines (CHM) when needed. https://yellowcard.mhra.gov.uk/idap

7. sources used for pharmacovigilance Spontaneous adverse drug reaction (ADR) reporting schemes like Yellow Card Scheme Clinical and epidemiological studies Worldwide published medical literature Pharmaceutical companies Worldwide regulatory authorities Morbidity and mortality databases Information collected through the Yellow Card Scheme is an important tool in helping MHRA and CHM monitor medicine safety

8. MHRA and Yellow Cards Yellow Card reports and other source of information and reports are evaluated, to determine whether any regulatory action is required to allow medicines to be used more safely and effectively. If the available evidence is insufficient at the time the issue would remain under close review as further data becomes available. If a new side effect is identified, information is carefully considered in the context of the overall side effect profile for the medicine, and how it compares with other medicines used to treat the same condition. More usually regulatory action can lead to restrictions in use, reclassification of the medicine, refinement of dose instructions or the introduction of specific warnings of side-effects in product information, which allow medicines to be used more safely and effectively.

9. lifecycle of a Yellow Card

10. Yellow Card report Suspect drug(s) - • route of administration • daily dose, dose frequency and schedule • dates of administration • if it is a vaccine, please quote brand and batch number Suspect reaction(s) - • when the reaction occurred • seriousness of the reaction • any treatment given • outcome of reaction Patient details - • patient sex • patient age at the time of the reaction • if known, please provide the patient’s weight • patient initials and a local identification number (hospital or practice reference number) to help you identify the patient in any future correspondence) Additional information - • other drugs taken in the last 3 months prior to the reaction, including over-the-counter (OTC) and herbal medicines • any information on re-challenge with the suspect drug(s) • relevant medical history, including allergies • relevant test results • for congenital abnormalities, please state all other drugs taken during the pregnancy and the date of the last menstrual period • attach additional pages (including print-outs of test results) if necessary Serious reactions - • are fatal • are life-threatening • are disabling or incapacitating • are congenital abnormalities • involve or prolong hospitalization • are medically significant

11. ADR Database Minimum required details — patient details, reporter details, name of suspect drug/medicine, and reaction—are present. All remaining information provided on the Yellow Card is then entered. A final quality audit step is carried out to ensure accuracy of the data.

12. Signal detection A signal is a possible causal relationship between an adverse event and a drug based on reported information. Usually more than a single report is required to generate a signal, depending upon the quality of the information. A signal is not a confirmed adverse reaction. Aim of signal detection - detect any possible unwanted effect associated with a medicine or to detect a change in the pattern or frequency of ADRs already known to be associated with a drug. Signal detection is the continual review of ADR reports to identify previously unrecognized or already associated concerns about medicines, vaccines or blood products, which may warrant further action.

13. Applications & Regulatory actions to minimize risk Information from all sources are carefully screened, identify unexpected ADRs lead to changes in the marketing authorization license of the medicine by MHRA with other European regulatory authorities, such as: Restricting the indications for use of a medicine Changes in the specified dose of the medicine Changes and introduction of specific warnings of side-effects in the product informationor on the package label Changing the legal status of a medicine, for example, from over-the-counter to prescription only In rare circumstances, removal of the medicine from the market, if the risks of a medicine are found to outweigh the benefits

14. Brief Pathways

15. Black triangle scheme New medicines and vaccines that are being monitored particularly closely by regulatory authorities in the European Union (EU) are described as being under 'additional monitoring'. New medicines and vaccines that are under additional monitoring have an inverted black triangle symbol (▼) displayed in their package leaflet and summary of product characteristic. It will not appear on the outer packaging or labelling of medicines. Black triangle means –should report all suspected ADRs for these products, it does not mean the medicine is unsafe. Medicines will be typically assigned a Black Triangle for a period of five years Appears in products like, British National Formulary (BNF), British National Formulary for Children (BNFC), Monthly Index of Medical Specialties (MIMS), Association of the British Pharmaceutical Industry (ABPI) Medicines Compendium, advertising material, Drug Safety Update, Summaries of Product Characteristics and Patient Information Leaflets - from Autumn 2013.

16. The Black Triangle Scheme for intensive monitoring of medicines has run for many years in the UK 2012 in EU – Introduced additional monitoring and the black symbol by new EU laws on the safety-monitoring of medicines, called the pharmacovigilance legislation After 1 September 2013 - New medicine are subject to additional monitoring will include the black symbol in the package leaflet and the summary of product characteristics when it is placed on the EU market European Medicines Agency (EMA) is responsible for maintaining the list of black triangle products. Assigned to a medicine - contains a new active substance, new medicines or vaccines authorized on or after January 2011, biological medicine, such as a vaccine or a medicine derived from plasma (blood), conditional approval, the company that markets the medicine is required to carry out additional studies: for instance, to provide more data on long-term use of the medicine, or on a rare side effect seen during clinical trials. Other medicines can also be placed under additional monitoring, on request from the MHRA or other regulators if the request is then approved by the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC)

17. ADR Data provision MHRA supplies anonymized case details (with reporter details removed and patient details anonymized) to pharmaceutical companies so they can perform safety analyses. Publish cumulative listings of all suspected ADRs received in listings are called Drug Analysis Prints (DAPs). These data are also used for answering enquiries on suspected adverse reactions from healthcare professionals and members of the public.

18. iDAP’s MHRA launched interactive Drug Analysis Profiles ( iDAPs ) on the Yellow Card website and provide suspected adverse reactions for all licensed drugs. These replace Drug Analysis Prints, which were previously available on the MHRA website. Each iDAP contains complete data for all spontaneous suspected adverse drug reactions, or side effects, which have been reported on that drug substance to the MHRA, via the Yellow Card Scheme from healthcare professionals, pharmaceutical companies and members of the public. Medicines are listed alphabetically by the name of the active ingredient, not by the brand name

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