The 3rd meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) was held in the Committee Room of the Drug Regulatory Authority of Pakistan (DRAP) on the 17th of September, 2023. The minutes of meeting are attached hereunder:-
Patient Safety
National Hazardous Waste Management Policy 2022
The National Hazardous Waste Management Policy, 2022 of Pakistan is a set of guidelines for the environmentally sound management of solid and hazardous waste in the country. The Ministry of Climate Change has formulated this comprehensive national level policy through consultative process with relevant stakeholders. This Policy is aimed at acting as an umbrella document to address the issue of hazardous waste.
Pharmaceutical Industry being a potential source of generating hazardous material as byproduct of its manufacturing, research and development processes. These involve handling of various chemical compounds which may be toxic, reactive, flammable or otherwise hazardous to human health and environment Therefore, proper management of hazardous waste in pharmaceutical industry is crucial to protect human health and environment.
The Drug Regulatory Authority of Pakistan (DRAP) in 167th meeting directed to upload the National Hazardous Waste Management Policy 2022 on its website for the information and awareness of pharmaceutical industry and other stakeholders.
Rapid Alert: Drug Product Recall: Incidents of loss and damage of vision with the off-label use of Avastin 100mg/4ml injection
Information Update on 3rd Nov, 2023: The recall of Avastin 100mg/4ml has been terminated based on the report of Central Drugs Laboratory, Karachi which declared the samples as of standard quality.
Rapid Alert
| DRAP Alert No | No I/S/09-24-36 |
| Action Date | September 24, 2023 |
| Target Audience | 1. Ophthalmologists and Endocrinologists 2. Healthcare Professionals – Physicians, Pharmacists, and Nurses. 3. Regulatory Field Force. 4. General Public |
| Problem Statement | Incidents of loss of vision in diabetic patients have been reported following treatment with Altered/Dispensed/Diluted Avastin injection. This product is approved by the Drug Regulatory Authority of Pakistan (DRAP) to treat Colorectal and other metastatic carcinomas. The use of this drug product in diabetic retinopathy or other ophthalmic conditions is one of the off-label uses and is not approved by DRAP. The incident is linked with the alteration/dispensing/dilution and sale of Avastin 100mg/4mL Injection under unhygienic/non-sterile conditions illegally and without any Drug Sale/Dispensing License (DSL) from Provincial Health Authority by M/s Genius Advanced Pharmaceutical Services Lahore. |
| Threats to Public Health | Avastin is a registered drug of M/s. Roche Pharma in Pakistan and is available in strength of 100mg/4ml and 400mg/16ml preparations. This drug is indicated for the treatment of colorectal and other metastatic carcinomas as a VGRF (vascular endothelial growth factor) inhibitor. However, the use in diabetic retinopathy is an off-label use to block the growth of abnormal blood vessels in the eye. Since this drug was being dispensed/diluted/repacked in 1.25mg/0.05ml dose under unhygienic conditions and in an unapproved manner, therefore, its safety cannot be ascertained which may lead to damage and loss of vision in the patients. |
The product identification details are as under: –
Therapeutic Goods Affected:-
Following is the detail of the alleged product:
| Product Involved | Manufacturer |
|---|---|
| Inj. Avastin 1.25 mg/0.05ml Composition: Bevacizumab Registration No. Nil | Genius Advanced Pharmaceutical Services. |
Following is the detail of DRAP approved product:
| Product Name | Suspected Batch | Manufacturer/Importer |
|---|---|---|
| Avastin 100mg/4ml Injection Composition: Bevacizumab Registration No. 043004 | H0352B11 B7266B20 B7266B07 | M/s Roche Diagnostics, Germany Importer: M/s Roche Pharma, Karachi. |
| Action Initiated | The Regulatory field force raided the premises of M/s Genius Advanced Pharmaceutical Services, Lahore, involved in the repacking and dispensing of Avastin injection under unhygienic/non-sterile conditions. The premises have been sealed and legal proceedings have been initiated against the personnel involved. The Importer of the registered product has been directed to recall the suspected batches of Avastin 100mg injection from the marked immediately. The sale/distribution of registered Avastin Injection has been put on halt till verification of its quality through sampling and laboratory testing to safeguard public health. Healthcare Professionals, Pharmacists and Chemists have been directed to stop the distribution, dispensing and administration of this product immediately, and check their stocks and stop supplying this product. The remaining stocks should be quarantined and returned to the supplier/company. |
| Advice for Healthcare Professionals | -DRAP requests increased vigilance at hospitals and within the supply chains of institutions/pharmacies/healthcare facilities regarding the off-label use of this product. -Adverse reactions or quality problems experienced with the use of these products shall be reported to the National Pharmacovigilance Centre (NPC), DRAP using Adverse Event Reporting Form or online through this link. -Please click here for further information on problem reporting to DRAP. |
| Advice for Consumers | Patients should not use this product for any ophthalmic disease and should contact their physician or healthcare provider if they have experienced any problem related to taking or using this drug product, and should report the incident to the Drug Regulatory Authority of Pakistan / National Pharmacovigilance Centre. All therapeutic goods must be obtained from licensed pharmacies and other authorized/licensed retail outlets. The authenticity and condition of products should be carefully checked. Seek advice from your pharmacists or other healthcare professionals in case of any doubt. |
The National Pharmacovigilance Center, DRAP urge the manufacturers and importers to nominate Pharmacovigilance Officer to ensure safe use of drugs.
Pharmacovigilance is the science and practice of monitoring the safety and efficacy of drugs, both before and after they are marketed. It is a vital aspect of ensuring public health and patient safety, as well as complying with regulatory requirements and ethical standards.
Pharmacovigilance officers are professionals who are responsible for collecting, analyzing, and reporting data on adverse drug reactions, drug interactions, and other potential safety issues. They also conduct risk assessments, implement risk management plans, and communicate with health authorities, health professionals, and patients.
The National Pharmacovigilance Centre at Drug Regulatory Authority of Pakistan urges the pharma industry to nominate or appoint pharmacovigilance officers for their products, as this will ensure the highest standards of quality and safety for their customers and patients. Pharmacovigilance is not only a legal obligation but also a social responsibility. Focusing on pharmacovigilance can enhance reputation, credibility, and competitiveness of a product in the global market.
According to the Pharmacovigilance Rules, 2022, notified by the Drug Regulatory Authority of Pakistan (DRAP), it is the legal obligation of the pharma industry to nominate or appoint a pharmacovigilance officer for products registered under the DRAP Act, 2012. The pharmacovigilance officer is required to perform the following duties:
- To collect, record, and report adverse events and other safety data related to the product to the National Pharmacovigilance Centre (NPC) within the specified time frame.
- To conduct periodic safety update reports (PSURs) and risk-benefit assessments of the product and submit them to the NPC.
- To implement risk management plans (RMPs) and risk minimization measures (RMMs) for the product as per the NPC’s recommendations.
- To ensure compliance with the pharmacovigilance rules and guidelines issued by the NPC and DRAP.
- To maintain pharmacovigilance records and documentation for at least 10 years.
“The NPC was established by DRAP in July 2022 under the Pharmacovigilance Rules, 2022, with the aim to enhance the pharmacovigilance activities in the country . The NPC is responsible for collecting, analyzing, monitoring, and preventing adverse effects of therapeutic goods, as well as reviewing and assessing safety data, conducting risk evaluations, and communicating with health authorities, health professionals, and patients. The NPC also provides training, guidance, and support to the provincial or regional pharmacovigilance centres, public health programs, and product registration holders.”
Consultative Workshop on Guidelines on Recalls and Rapid Alerts of Defective Therapeutic Goods
National Regulatory Authorities are responsible to ensure that recalls are handled properly and promptly, including alerting the public, classifying the type of drug recall, and safely removing the affected product from the market. DRAP in collaboration with WHO, organized one-day consultative workshop on “Guidelines on Recalls and Rapid Alerts of Defective Therapeutic Goods” held at DRAP Headquarter in Islamabad on 20th July, 2023. The workshop was aimed at ensuring strong communication skills and knowledge to effectively handle the SF threat and execution of recalls and rapid alerts. Government Analysts from all Quality Control Laboratories (QCLs) working under the DRAP Act 2012 and Drug Act 1976, as well and representatives from drug control administration of all federating units participated in the workshop.
The workshop focused on the following key objectives:
- Implementation of effective and integrated Recall and Rapid Alert system in Pakistan.
- Emphasizing the need and importance of Recall and Rapid Alert System.
- Training and building capacity of all the participants.
- Enhancing coordination and communication with provincial governments and related departments.
- Safe disposal system of SF products
- Improvement in DRAP’s guidelines and harmonization with International best practices.
Core Activities and Topics Covered
1. Introduction and Objectives of Workshop The day began with an overview of current system for rapid alerts and recalls for removing defective therapeutic goods from the market. Director Quality Assurance and Lab Testing, DRAP briefed the participants on the strategies designed to strengthen the collaboration among regulators and QCLs of all federating units. He emphasized the importance of timely and accurate communication to combat the challenge of SF therapeutic goods.
2. Overview of DRAP’s guidelines on Recalls and Rapid Alerts of Defective products This session explained the guidelines of DRAP and action response currently opted by DRAP, highlighting its strengths and limitations. Participants engaged in group discussions to evaluate which methods would be most effective in different scenarios.
3. WHO recommendation on Recalls and Rapid Alerts System in the benchmarking visit Participants were introduced to the WHO GBT indicators, sub-indicators and IDPs, WHO recent visit and their recommendation for the improvement of the current Rapid Alert system. The trainer comprehensively delivered the details, ensuring that the information provided is easily comprehensible and actionable.
4. Harmonization of Terminologies for Defective Products and Role of QCLs in Detection and Disposal of SF products This segment focused on the terminologies being used nationally and their harmonization with WHO recommended terminologies. Later the role of Quality Control Laboratories was emphasized and discussed in group discussion.
5. Best practices for storage and disposal of SF products This session highlighted the current available practices and international practices as recommended by the WHO for safe storage and disposing of the SF products.
6.Effective communication among stakeholders for their removal from the market ;Recall is an effective means of protecting the public from a defective or potentially harmful product, and strong communication among relevant stakeholders is essential for the effective recall of SF Products. It was suggested to utilized modern communication channels by all federating units to ensure in time action on trigger information to safeguard public health. It was agreed by all the participants that prompt and effective communication is very crucial for implementing an proficient Rapid Alert and Recall System to removal of SF product from markets.
7. Practical Exercises The afternoon session involved hands-on practical exercises. Participants were divided into groups and tasked with case studies for different hypothetical scenarios. Case studies and simulations illustrated the effective collaboration between all the relevant stakeholders. This interactive exercise encouraged teamwork and allowed attendees to apply the concepts learned throughout the day.
8. Concluding Remarks and Distribution of Certificates Director Pharmaceutical Evaluation & Registration (PE&R) concluded the workshop with his closing remarks on appreciating the active participation from all regulatory entities and QCLs across Pakistan. The certificates of participation were distributed among the participants at the end of session.
Recall Alert: Drug Product; Spadix Injection (Batch# 570) by M/s. Tabros Pharma Karachi
Recall Alert
| DRAP Alert No | NoI/S/20-23-21 |
| Action Date | 20th April 2023 |
| Target Audience | 1. Pharmacists and Chemists at Distributions, Pharmacies and Medical Stores 2. Healthcare Professionals- Physicians, Pharmacists, and Nurses at Hospitals, Clinics and Healthcare Providing Institutions 3. General Public |
| Product(s) Affected | Spadix 4mL Injection Composition: Phloroglucinol and Trimethylphloroglucinol Manufactured by: M/s. Tabros Pharma, (Pvt) Ltd., Karachi Batch No. 570 |
| Problem / Issue | A video is circulating on social media regarding presence of a fly/insect in a liquid injection ampoule visible with naked eye, apparently seems to be having adulterated quality. The matter is still under investigation, however as a precautionary measure, to prevent any public health hazard, the alleged drug is being recalled from market. |
| Risk Statement | Drug Product contains fly/insect is of adulterated quality which may compromise the standard quality of drugs as not being sterile. The sterility is a basic quality attribute of all Injectable drugs. In this case such adulterated drug may initiate but not limited to following reaction in patients/users (i) Anaphylactic shock in patients which may lead to death of patient (ii) Skin rashes, itching, difficulty in breathing (iii) Sub optimal to no therapeutic effect for indicated medical treatment. |
| Action Initiated | -The manufacturing company / registration holder has been directed to immediately recall the defected batch of product from the market. -All Pharmacists and chemists working at distributions and Pharmacies should immediately check their stocks and stop supplying this batch of product. The remaining stock should be quarantine and return to the supplier / company. -Distributors and pharmacies are advised to be vigilant and report any suspected batch of product(s) in the supply chain to the DRAP using online form, or through phone at +92 51 910 73 17, or Email at gsms∂dra.gov.pk. -Regulatory field force of all federating units (DRAP, Provincial Health Departments and States) has also increased the surveillance in the market to ensure the effective recall of defective product(s). |
| Advice for Healthcare Professionals | -DRAP requests increase vigilance within the supply chains of healthcare institutions and hospital pharmacies to identify and return the defective batch(es) of this product to the importer / company. -Adverse reactions or quality problems experienced with the use of this product may be reported to the National Pharmacovigilance Centre(NPC), DRAP using Adverse Event Reporting Form or online through this link. -Please click here for further information on problem reporting to DRAP. |
| Advice for Consumers | -Consumers should stop using this product bearing the affected batch number(s) and shall contact to their physician or healthcare provider(s) if they have had experienced any problem that may be related to taking or using this product. -All drug products must be obtained from the authorized licensed pharmacies /outlets. Their authenticity and condition should be carefully checked. If you have any doubt, please seek advice from your pharmacist. |
Drug Safety Alert: Potential risk of suicidal ideation/thoughts & self-injury with Finasteride
Drug Safety Alert
Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan
| Date: | 11th of April, 2023 |
| Target Audience: | • Manufacturers and importers of Finasteride; • Healthcare Professionals; and • Patients, consumers or caregivers. |
| Background: | The Health Sciences Authority (HSA) of Singapore in August 2022 reminded healthcare professionals of the potential risk of suicidal ideation with the use of finasteride following results of a recent pharmacovigilance study that suggests younger patients with alopecia may be more vulnerable to the risk of suicide ideation. In the study, disproportionality analysis was used to assess whether suicidality or psychological adverse events (AEs) were more frequently reported for finasteride than would be expected by chance alone by comparing them against similar reports for all other drugs in VigiBase (WHO global database of ICSRs). The study identified 356 reports of suicidality and 2,926 reports of psychological AEs in users of finasteride, reported from 1993 to 2019. Among the reports with data available, the majority (99%) occurred in males, and 71% occurred in individuals aged between 18 and 44 years. Significant disproportionality signals for suicidality (reporting odds ratio [ROR], 1.63; 95% CI, 1.47-1.81) and psychological AEs (ROR, 4.33; 95% CI, 4.17-4.49) were identified in finasteride users. On 19th of January, 2023, Health Canada through its summary safety review informed that it is working with the manufacturers to update the product safety information in the Canadian product monographs (CPM) for finasteride-containing products to strengthen the warning statements on the risks of suicidal ideation and self-injury, and to include information about patient screening for psychiatric risk factors prior to starting treatment, as well as continuous patient monitoring during and after stopping treatment. The safety review was triggered by the publication of a media article that discussed the potential risk of suicide in patients using Propecia (finasteride) for male pattern hair loss. Health Canada’s review of the available information found a possible link between the use of finasteride and the risks of suicidal ideation and self-injury. At this time, there is not enough information to establish a link for the risk of suicide. However, strengthening of warning statements was warranted. It was informed that Health Canada was monitoring the risk of suicidal ideation with the use of finasteride since 2012 and has completed 2 safety reviews in 2012 and 2015, and the information available at the time was considered too limited to determine whether there was a link between the use of finasteride and suicidal thoughts and behaviours (suicidality). In 2019, following reports of Canadian and international cases of suicide, suicidal ideation and self-injury with the use of finasteride, the agency completed a third safety review that found a possible link between finasteride and the risk of suicidal ideation. The CPMs of finasteride were accordingly updated to include the risk of suicidal ideation. Most recently in 2022, due publication of a media article that discussed the potential risk of suicide in patients using Propecia (finasteride) for male pattern hair loss, Health Canada completed a review of the risk of suicidal ideation and potential risks of suicide and self-injury with the use of finasteride. The purpose of the current review was to consider recent information and determine if additional measures were warranted. A review of the available information found a possible link between the use of finasteride and the risks of suicidal ideation and self-injury. At this time, there is not enough information to establish a link between the use of finasteride and the risk of suicide. Therefore, strengthening of warning statements on the risks of suicidal ideation and self-injury was warranted and Health Canada is working on it. Furthermore, the most recent Vigilyze statistics related to the finasteride and Standard MedDRA Query(SMQ) selected Depression and suicide/self-injury study identified 2,995 reports and 471 reports specifically with suicidal ideation. The larger portion of the reactions in known gender occurred in males (31.9%, and 45.6% in individuals aged between 18 and 44 years respectively, with the broader SMQ and specifically suicidal ideation. Significant disproportionality signals for suicidal ideation (reporting odds ratio [ROR], 10.6) and SMQ (ROR, 4.5) were identified. |
| Therapeutic Good(s) Affected: | Name: Finasteride. Finasteride is indicated for the treatment of benign prostatic hyperplasia and androgenic alopecia. |
| Action in Pakistan | Accordingly, the case of the potential risk of suicidal ideation/thoughts & self-injury with finasteride was discussed in the 2nd meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the National Pharmacovigilance Centre (NPC), Division of Pharmacy Services, Drug Regulatory Authority of Pakistan (DRAP), which decided as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 that registration holders should update prescribing information/safety specification of finasteride containing drugs by strengthening the warning statements on the risks of suicidal ideation and self-injury, and to include information about patient screening for psychiatric risk factors before starting treatment. |
| Advice for healthcare professionals: | Healthcare professionals are informed that mood alterations including depression and, less frequently, suicidal ideation have been reported in patients treated with finasteride and are hereby advised to consider the potential risk of psychological adverse events when assessing the benefit-risk of finasteride for their patients. Healthcare professionals should also advise their patients to consult their doctors at the earliest when such thoughts are developed. |
| Advice for patients: | Patients are advised to immediately consult their doctors if they experience mood alterations including depression and less frequently, suicidal ideation or self-injury etc. |
| Guidelines for reporting Adverse Drug Reactions (ADRs): | Both healthcare professionals and patients are requested to report any suspected Adverse Drug Reaction (ADR) to National Pharmacovigilance Centre, Drug Regulatory Authority of Pakistan through Med Vigilance E-Reporting system available on DRAP website. Similarly, ADRs can also be reported through MedSafety App that is available for download from App store (for iOS devices) and Google Play (for Android devices). |
| References: | Minutes of 2nd meeting of Pharmacovigilance Risk Assessment Expert Committee. |