Stakeholders Comments are invited on revision of Guidelines on Conduct of Clinical Trials in Pakistan

The Drug Regulatory Authority of Pakistan (DRAP) is revising Guidelines on Conduct of Clinical Trials in Pakistan with the aim to ensure the safety, quality, and efficacy of investigational products in clinical trials, as well as the ethical conduct and oversight of clinical research in Pakistan.

The revised guidelines cover various aspects of clinical trial activities, such as:

  • The regulatory framework and approval process for clinical trials in Pakistan
  • The roles and responsibilities of various stakeholders involved in clinical trial activities, such as DRAP, National Bio Ethics Committee, sponsors, investigators, and pharmaceutical associations
  • The requirements and procedures for obtaining informed consent, protecting the rights and welfare of trial participants, and reporting adverse events and serious adverse events
  • The standards and principles for designing, conducting, monitoring, recording, analyzing, and reporting clinical trials
  • The good clinical practice (GCP) requirements for clinical trial materials and investigational products
  • The data management and quality assurance systems for clinical trial data and documents
  • The post-trial obligations and follow-up measures for clinical trial sponsors and investigators

The revised guidelines are based on the best regulatory practices as per the International Council for Harmonisation (ICH) guidelines, and the World Health Organization (WHO) guidelines.

The revised guidelines are open for public comments until February 22, 2024. DRAP invites all the relevant stakeholders, such as pharmaceutical companies, research institutions, clinical trial organizations, health professionals, patient groups, and civil society organizations, to review the revised guidelines and provide their feedback and suggestions. Stakeholders can submit their comments and suggestions using prescribed format (click here to visit how to submit comments) via email to shafqat.hussaindra.gov.pk or can be posted at mailing address, Director, Division of Pharmacy Services, Drug Regulatory Authority of Pakistan, PM health Complex, Park Road, Islamabad.

DRAP appreciates the cooperation and contribution of all the stakeholders in the development and improvement of the guidelines on conduct of clinical trials in Pakistan. DRAP hopes that the revised guidelines will facilitate and promote the conduct of high-quality, ethical, and reliable clinical trials in Pakistan, and ultimately benefit the public health and well-being of the people of Pakistan.


Warning To Therapeutic Goods Manufactures on DEG/EG Impurities in Raw Materials: A Serious Threat to Therapeutic Goods Quality and Safety

The Drug Regulatory Authority of Pakistan (DRAP) has issued a warning to the therapeutic goods industry about the use of raw material contaminated with diethylene glycol (DEG) and ethylene glycol (EG) impurities, which can pose serious health risks to consumers.

What is the issue?

The Central Drugs Laboratory Karachi has declared another sample of raw material i.e. propylene glycol (PG) as substandard sent for test/analysis due to unacceptable levels of ethylene glycol.

Propylene glycol, sorbitol and glycerin are used as solvents in the manufacturing of oral liquid preparations in the pharmaceutical and alternative medicines industry. When used in oral liquid preparations, these solvents can lead to serious health risks due to DEG and EG toxicity. When ingested, DEG and EG are metabolized into toxic metabolites that can affect the central nervous system, heart, and can cause kidney damage, which can be fatal.

In the past two years, there have been international reports related to the adulteration of these raw materials with DEG and EG causing kidney damage and death of children in Gambia, Uzbekistan, and Indonesia. Industrial grade DEG and EG are used for various applications (solvents, antifreeze agent) in other industries.

Earlier, several cases of substandard raw materials including PG and finished goods contaminated with DEG and EG have been reported from various part where investigations have suggested that the main problem lies with the integrity of supply chain of raw material which appears to be compromised. Consequently, action has been initiated against the culprits involved.

What are the actions taken by DRAP?

Despite repeated warnings and instructions, many therapeutic goods manufacturers have neglected to verify the quality and safety of their raw materials from authorized vendors. The Central Drug Laboratory, Karachi is currently analyzing both raw materials and finished products for EG and DEG contamination, following the pharmacopoeial standards and WHO guidelines for testing of EG and DEG in oral liquid preparations. To ensure the quality and safety of their products, manufacturers should test their raw materials for EG and DEG contamination before using them in their production processes to prohibit potential influx of contaminated products in the market.

In view of the criticality of the matter and potential for untold human tragedy, the therapeutic goods industry is once again warned to screen raw materials (propylene glycol, glycerin and sorbitol) for contamination with EG and DEG before using these materials in the manufacturing of oral liquid preparations. Additionally, all finished products must be analyzed for EG and DEG contamination before their release into the market. DRAP also issued directives to nutraceutical and alternative medicine companies to ensure compliance and safeguard public health from contaminated products. Additionally, the industry is diected to recall any finished products that were manufactured using the contaminated lot/batch of propylene glycol, hold the affected batches of finished products and ensure testing of finished products for EG and DEG contamination before releasing them into the supply chain.

DRAP urge pharma industry to take measures to prevent utilization of contaminated raw material in the manufacturing of liquid preparation including following:-

  • Implement a supplier qualification and verify the compliance of the suppliers with the relevant standards and regulations.
  • Verify traceability and authenticity of the raw material using unique identifiers such as barcodes or RFID tags to track their movement and origin throughout the supply chain.
  • Conduct regular risk assessments and monitor the performance of the suppliers, and take corrective actions if any issues are detected.
  • Educate and train the staff and the suppliers on the importance of preventing EG and DEG contamination, and the potential consequences of using contaminated solvents.
  • Verify the features that indicate the authenticity of the product, such as holograms, serial numbers, watermarks, or special packaging. The products should also be checked for any signs of poor printing, misspellings, inconsistent logos, tamper-evident seals or sturdy wrapping materials.

DRAP is committed to ensure the safety and quality of therapeutic goods in Pakistan, and protecting the public from substandard and falsified products.

Registration Board Direction; Procedure for Capacity Assessment of the Contract Acceptor

Registration Board in its 333rd meeting held on 19th – 20th December, 2023 discussed the subject mentioned case and decided as under: –

1.         Inspection of contract accepter for manufacturing / testing capacity assessment shall be conducted for all those contract manufacturers, who has not been inspected for such purpose with in the last 3 years. The panel shall verify capacity assessment of all those sections, which are approved by the Licensing Division.

2.         Capacity assessment of newly applied facility (Section) shall not be carried out, if any section of that manufacturing facility has already been assessed within last three years.

3.         Following shall be prerequisites for submission of application for contract manufacturing under Rule 20(A) of Contract Manufacturing Policy.

a.         Affidavit on stamp paper (Showing name, designation, CNIC Number of contract giver) stating installed capacity of the contract accepter for contract manufacturing. This affidavit shall only be signed by the CEO / MD of the firm. i.e. contract accepter.

b.         Copy of DML of both firms. i.e. contract giver and contract accepter along with Section (s) approval from Licensing Division.

c.         Valid GMP certificate or GMP inspection report of the contract accepter, conducted within last three years.

d.         Copy of legalized contract between contract giver and contract accepter on stamp paper presenting the capacities of the contract accepter for the manufacturing sections for whom the products have been applied, and

4.         Affidavits submitted by the contract accepter, showing manufacturing / testing capacity, will be verified in the subsequent inspections conducted for GMP / renewal of DML and will be reported accordingly. Chairman, Registration Board may constitute panel of experts to verify capacity assessment, if required.

5.         The capacity verification report will be valid for 3 years.

Guidelines on Standards for Establishment of Hospital Pharmacies is now open for comments.

Drug Regulatory Authority of Pakistan is seeking feedback on proposed guidelines for hospital pharmacies. These standards aim to ensure consistent, high-quality pharmacy services across all hospitals, ultimately benefiting patients and the healthcare system as a whole.

The guidelines cover four key areas:

  1. Hospital Pharmacy Operations which include aspects like organizational structure, staffing, resources, policies, and procedures for managing medications from procurement and storage to dispensing and monitoring.
  2. Medicine Use Management where the focus is on optimizing medication use within the hospital. This involves procedures for medication reconciliation, identifying potential issues, and implementing strategies to improve medication effectiveness and avoid medication-related harm.
  3. Quality Improvement with the believe in continuous improvement! These guidelines outline practices for assessing the effectiveness of hospital pharmacy services, identifying areas for improvement, and implementing corrective actions.
  4. Human Resources Development for ensuring a competent and skilled pharmacy workforce is crucial. The guidelines address training and development programs for all pharmacy personnel, from pharmacists to technicians.

DRAP invites you to review the proposed guidelines and share your thoughts and suggestions. Your input will be invaluable in shaping the final document and ensuring it reflects the needs and expectations of patients, healthcare professionals, and the community.

These guidelines were uploaded on the official website of DRAP on 12th of January, 2024 for seeking comments and suggestions from stakeholders on the draft document. Stakeholders can submit their comments and suggestions within 15 days of uploading this document using prescribed format. For further guidelines on how to submit comments visit DRAP website or click here. Comments and suggestions can be forwarded via email to dir.psdra.gov.pk, copying aqsa.hashmidra.gov.pk, or can be posted at mailing address, Director, Division of Pharmacy Services, Drug Regulatory Authority of Pakistan, 3rd floor TF Complex, 7th Mauve Area, G-9/4, Islamabad.

Press Release: Toxic Impurities Found In Raw Material; DRAP Directs Oral Liquid Manufacturers To Ensure Testing Of Raw Material For Imurties

Islamabad, January 11, 2024 — The Drug Regulatory Authority of Pakistan (DRAP) has issued a warning to the therapeutic goods industry about a batch of propylene glycol raw material that has been found to be contaminated with ethylene glycol, a toxic substance that can cause serious health problems and even death.

The report of Federal Government Analyst at Central Drug Laboratory, Karachi has revealed ethylene glycol contamination in the said batch of propylene glycol, in an amount much higher than the acceptable limit. The contaminated batch (C815N30R41) was claimed to be manufactured by Dow Chemicals, Thailand. Initial investigations suggest that the integrity of the supply chain of the raw material may have been compromised.

Propylene glycol, sorbitol and glycerin are used as solvents in the manufacturing of oral liquid preparations in the pharmaceutical and alternative medicines industry. In the past two years, there have been international reports related to the adulteration of these raw materials with Diethylene glycol (DEG) and Ethylene glycol (EG) causing kidney damage and death of children in Gambia, Uzbekistan, and Indonesia. Industrial-grade DEG and EG are used for various applications (solvents, antifreeze agent) in other industries.  

DRAP has directed the pharmaceutical companies to immediately recall finished products from local and export markets that were manufactured using the mentioned batch of propylene glycol. The Regulatory Field Force has been instructed to confiscate the contaminated batch of propylene glycol, seize all oral preparations that were manufactured using the same batch of propylene glycol and submit the report within 24 hours. DRAP has also directed the therapeutic goods industry to hold finished products manufactured from any other lot of propylene glycol claimed to be manufactured by Dow Chemicals, Thailand and ensure testing of finished products for EG/DEG contamination before releasing them into the supply chain.

The Central Drug Laboratory in Karachi is currently conducting analysis of both raw materials and finished products against the pharmacopoeial monograph and WHO guidelines for testing of EG/DEG in oral liquid preparations, respectively, as a part of the ongoing investigation.

In December 2023, DRAP issued its third advisory to the pharmaceutical industry, requiring companies to screen raw materials for contamination with EG and DEG before using them in the manufacturing of oral liquid preparations. Additionally, all finished products must be analyzed for EG/DEG contamination before their release into the market. DRAP also issued directives to nutraceutical and alternative medicine companies to ensure compliance and safeguard public health from contaminated products.

DRAP is committed to ensure the safety and quality of therapeutic goods in Pakistan, and protecting the public from substandard and falsified products.

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DRAP’s Pharmacovigilance Newsletter (December, 2023 ; Issue-II)

The Pharmacovigilance Newsletter is a quarterly publication that aims to inform and educate the healthcare professionals and the public about the importance of pharmacovigilance and adverse drug reaction reporting. It also showcases the activities of the National Pharmacovigilance Centre (NPC) and initiatives taken by the NPC for monitoring and evaluating the safety of medicines in Pakistan.

We are pleased to announce that the second issue of the Pharmacovigilance Newsletter (Dec-2023) is now available for download from our website. This issue covers the latest updates on the safety of medicinal products and regulatory actions taken by the Drug Regulatory Authority of Pakistan (DRAP) and other international authorities.

We hope that you will find the newsletter informative and useful. We welcome your feedback and suggestions for improvement. You can contact us at npcdrap.gov.pk or call us at +92-51-9255980. Thank you for your interest and support in pharmacovigilance.

Together, we can ensure the safe and effective use of medicines in Pakistan.

DRAP Participating in International Med Safety Week 2023 Social Media Campaign

From 6 to 12 November, Drug Regulatory Authority of Pakistan (DRAP) will take part in the global #MedSafetyWeek campaign, a collaboration involving more than 80 medicines regulatory agencies and several non-governmental organizations, to raise awareness about the importance of reporting side effects of medicines. With the theme ‘Who can report?’, this year’s campaign will focus on the key role of every patient, doctor, nurse, and pharmacist who reports a side effect and contributes to using medicines safely.

DRAP seek your support to enhance reporting of adverse drug reactions (ADRs) to ensure medicines on the market are acceptably safe.

Reports about side effects can be submitted easily through Med Safety App, DRAP med Vigilance e-reporting system or yellow reporting form.

For detail on how to report visit the link.

#MedSafetyWeek2023

Play your part in medicines safety. Whether you’re a patient, doctor, nurse, or pharmacist, you can help make medicines safer by reporting side effects to National Pharmacovigilance Centre, DRAP.

Through the #MedSafetyWeek campaign more than 80 countries will work together to improve the safety of medicines globally

All medicines agencies operate systems to detect and analyse side effects of medicines. The purpose of safety monitoring is to gain more information about known side effects and find out about new ones. Constantly collecting and monitoring information from the reports received helps identify risks associated with medicines and take action to minimise harm.

#MedSafetyWeek is an international campaign of Uppsala Monitoring Centre (UMC).

The campaign is supported by WHO and by members of the International Coalition of Medicines Regulatory Authorities (ICMRA)

DRAP emphasizes the importance of reporting side effects through Med Safety App, DRAP med Vigilance e-reporting system or yellow reporting form. All reports made to National Pharmacovigilance Centre (NPC) DRAP will be thoroughly assessed and examined to determine the right steps to be taken to protect the population from harm. Since 2018, NPC DRAP has received and processed over 30,000 reports in which patients, carers, and healthcare professionals have played a key role

“Every report is important in building more knowledge and understanding of the benefits and risks of medicines in clinical use and allows action to be taken to minimise risks.

“Reporting suspected side effects to the NPC DRAP helps to make medicines safer for patients all around the world. In some cases, it can result in better prescribing advice, which can improve patient outcomes.

“If you, or a patient you are supporting, experience a side effect with a medicine, make sure to report it to us promptly.”

Dr.Obaidullah,

National Pharmacovigilance Centre, DRAP, Pakistan