Post Market Surveillance KNH/UON Pharmacy Symposium Optimizing Medicine use to Improve Patient Outcome Edward Abwao Pharmacy and Poisons Board 16th May 2014

Post Market Surveillance: Definition Post-market surveillance refers to all the processes that are carried out to continuously track/ monitor quality, safety and efficacy of medicines in the market (after registration).

Why Post Market Surveillance? Medicines do not necessarily retain their quality, safety, efficacy after registration over their shelf life. Several factors from shipment, warehousing, distribution and eventual dispensing to patients such as handling and storage conditions can affect quality of the medicines. Some people can compromise on these factors and inherent quality of medicine by adopting unethical business practices. Varying climatic conditions in the country may affect quality of medicines.

Post Market Surveillance: Importance PMS ensures that, even after registration, drugs continue to meet the required standards whilst in the market.

Post Market Surveillance System It involves active and reactive PMS. Active PMS refers to: coordinated surveys, sampling and analysis, evaluation and assessment of regulatory requirements in relation to labeling, storage etc Reactive PMS refers to: follow up on complaints from spontaneous reporting

The regulatory actions taken included; Recall Quarantine During the life of a product in the market, quality issues may arise necessitating regulatory action to be taken. The regulatory actions are taken to ensure that the products meet quality, safety and efficacy as per requirements of the law. PPB takes action to ensure that public is not harmed by the continued use of products under investigation. The regulatory actions taken included; Recall Quarantine Suspension of marketing authorization Withdrawal Edward Abwao

In our Pharmacovigilance and Post-Market Surveillance activities We can all appreciate there is a place for Regulatory Actions to be undertaken These need to be undertaken at the soonest in many cases to avoid greater potential harm that the poor quality medicine can inflict on its consumer However, actions need to be based on facts, ‘proof’ and/ or reports of potential to cause harm Jayesh- Pharmacovigilance

Jayesh- Pharmacovigilance Summary of findings… PMS of Anti-TB Medicines: 1 product unregistered 8% (10/120) failed: assay… all over 110% upper mark PMS of Antiretroviral Medicines: 27% (26/95) unregistered 0.37% (1/274) failed analysis: uniformity of weight* PMS of Antimalarial Medicines: 6% (36/536) samples unregistered 16% (7/44) samples failed lab compendia analysis Jayesh- Pharmacovigilance

Common Regulatory Problems Unregistered products found in the market Poor quality medicines found in the market Storage of medicines in public health facilities wanting Jayesh- Pharmacovigilance

Common Regulatory Actions on PMS Step wise: Unregistered medicines identified Poor quality medicines identified (lab analysis, mini-lab tests) Letters to implicated manufacturers and distributor of the said products issued to quarantine and recall product(s) Product(s) withdrawn from the market “Pharmacovigilance E-shot” sent out Jayesh- Pharmacovigilance

Common Regulatory Actions on PMS (2) Implicated company pharmacists summoned to Practice / Enquiries and Disciplinary Committee of PPB Inspection of cGMP enhanced Closure of pharmaceutical manufacturer / distributor Continued vigilance of medicines implicated Newsletters published and disseminated widely with alert of the medicines Consumer awareness Jayesh- Pharmacovigilance

Examples of some of the recalls include A medicine or a particular batch may be removed from the market due to safety , quality or efficacy concerns. Recall can be voluntary or initiated by PPB Poor quality Paracetamol tablets Poor quality Benzypenicillin Scheriproct ointment B-Immune sachets Diuride 20mg Typhim Vi® (Typhoid vaccine) by Sanofi Pasteur Polaramine expectorant Edward Abwao

Examples of quarantine Darrow’s solution Hartman’s solution Dextrose 5% Oxytocin injections HES containing solutions Edward Abwao

Examples of withdrawals This involves revocation or cancellation of the marketing authorization by PPB. This is mainly done due to safety concerns but can also b due to quality and efficacy issues. Nimesulide tablets Vioxx (Rofecoxib)- incrased risk of cardiovascular events Chlorproguanil + Dapson (Lapdap)- anemia in G-6-PD deficient patients Thalidomide Edward Abwao

Rescheduling Policy Change This can be done to move medicines from POM, OTC E.g SPs moving from POM to OTC Chloroquin rescheduled from OTC to POM Policy Change E.g putting patients on TDF instead of D4t due to the safety concerns Edward Abwao

Jayesh- Pharmacovigilance Brand Name Active Ingredient Manufacturer Batch No. Reason for Recall Ultracaine Heavy Injection Bupivacine HCl 5mg and Dextrose 80mg/mL Jayson Pharmaceutical Ltd, Bangladesh All batches Complaints on lack of efficacy; Products failed analysis Minyua Oral Suspension Mebendazole 200mg/5mL Cosmos Ltd, Kenya 100299 Caking of suspension Amoebazole Suspension Metronidazole Sphinx Pharmaceuticals, Kenya 0251M Crystallization of suspension Paracetamol Tablets Paracetamol 500mg Ningbo Shuangwei Pharmaceutical Co. Ltd 081201, 090106, 081254, 081219 Moulding and Discolouration HePBQuin Injection Hepatitis B immunoglobulin Sanquin, Netherlands 08K20H506A Package insert not complying to PPB requirements Rihide-P Paediatric Tablets Rifampicin 60mg/ Isoniazid 30mg Cosmos Ltd 080648, 080650, 080652 Products failed quality analysis Ethambutol/ Isoniazid Tablets Ethambutol 400mg/ Isoniazid 150mg Svizera Europe BV SL836, SL889 Gentamicin Injection Gentamicin 20mg/mL Dawa Ltd, Kenya 0710304 Non-compliance to labeling requirements Augpen Oral Suspension Amoxicillin / Clavulanate potassium 156mg/5mL Emcure Pharmaceuticals Ltd, India PFA 09008 Change of colour Jayesh- Pharmacovigilance

Reason for mopping out of the market and destruction Brand Name Manufacturer Reason for mopping out of the market and destruction Co-Malasin Tablets Dawa Ltd, Nairobi, Kenya Unregistered Arsun-AQ Tablets Arex Suspension Gesto Pharmaceuticals Ltd Lum-artem Oral Suspension Co-fantrin Tablets Comet Healthcare Ltd Daquinex Oral Solution Artecure Tablets Mepro Pharmaceuticals Ltd Comether Tablets Pharma Link Laboratories Pharmasidar Tablets Shanghai Pharmateq Artefantrine Tablets NBSW Pharma Ltd Quinine Tablets Urnav B.V. Spectino 2g Injection Dawa Ltd, Kenya

Various PV sensitizations

www.pv.pharmacyboardkenya.org PPB has also developed and launched an online reporting system that allows both the healthcare worker and consumers of medicines to submit a report on any suspected poor quality medicine or suspected adverse drug reaction. Developed Pharmacovigilance e-shot (an electronic mailing system used to communicate to subscribers issues of concern) Also for clinical trials www.ctr.pharmacyboardkenya.org

Launch of PVERS

AL CEM Launch

PV Training of UoN final year students

Specific Activities (2) Introduction of mini-lab screening for antimalarials Scale up to ARV and anti-TB medicines currently ongoing Development of a Post Market Surveillance Strategy (PMS) for Kenya Collaboration with WHO, USAID and other partners Collaboration with INTERPOL and ACA on SSFFCs

Returns from our activities Poor quality medicinal products complaints received: “Caking Not-flowing Moulding Laminating Floating particles Crystalization Corrosion of Al covers Change of colour Poor coating Chipping Poor packaging Expired medicines Lack of efficacy Suspected counterfeits Un-registered products...”

Ever seen this?

Challenges Lack of enough funds Fewer members of staff Delays in getting laboratory analysis results Politics Unscrupulous businessmen/ professionals Under reporting – most cases are not reported Consumer reporting for suspected ADRs and Poor Quality Medicines

Thank you very much

Our contact … Lenana Road Directorate of Medicines Information and Pharmacovigilance Pharmacy and Poisons Board Lenana Road P.O. Box: 27663-00506 Tel: +254-(020) 3562107 Nairobi KENYA 2716905/6 Fax: +254-(020) 2713431 / 2713409 e-mail: pv@pharmacyboardkenya.org www.pharmacyboardkenya.org