The second volume of quarterly Newsletter of DRAP was issued on 1st January, 2023. This issue highlights the key initiatives and accomplishments of the outgoing year-2022, and welcomes the new year-2023 with reaffirmation to its commitments. DRAP is implementing its Strategic Plan 2022-25 with full zeal and devotion, to protect the public health through effective regulation for availability of safe, quality assured and efficacious therapeutic goods for the people of Pakistan.
Regulatory Updates
Testing of Diethylene Glycol (DEG) & Ethylene Glycol (EG) at Central Drug Laboratory, Karachi
The Central Drug Testing Laboratory (CDL), Karachi, is providing facilities for testing of solvents (Glycerin, Propylene Glycol, and Sorbitol) used in oral preparations for the presence of any toxic impurities (e.g., Diethylene Glycol (DEG) and Ethylene Glycol (EG)) to the manufacturers and importers of pharmaceutical products. DRAP has already issued advisories and directions via letter F. No. 6-30/2022-QA dated October 21, 2022 and December 13, 2022 to the stakeholders for compliance.
Central Drug Laboratory has issued following guidance steps for manufacturers and importers for availing these facilities.
Sampling:
- Sampling should be made on the basis of √n + 1
- A composite of the quantity drawn should be made
- Divide this composite in three equal parts (approximately 30ml in each bottle)
Fee:
- Fee voucher to be generated on DRAP’s fee portal fee.dra.gov.pk by completing following steps:-
- a. Create Login / Enter Your Login Details
b. Click on Generate Fee
c. Select Division = Central Drugs Laboratory
d. Select Payment Head = Central Drugs Testing laboratory
e. Fee = Gas Chromatography
f. Enter Details - Fee for each batch is Rs.23000/-
Document Required:
- Sampling Information Sheet.
- Certificate of Analysis by Manufacturer.
- Testing Request Letter.
- Copy of voucher paid in any branch of Allied bank.
Testing Time:
- The samples will be tested on the FIFO basis.
Dispatch of Samples
- Three bottles as mentioned under sampling per batch shall be sent to CDL along with the
documents mentioned above. - The firm is responsible to maintain the conditions of samples during transportation.
- Sample should be dispatch on following Address:-
Director, Central Drugs Laboratory
4-B, SMCHS, Block B, Karachi
For any further assistance, Please contact to
Director, Central Drugs Laboratory, 4-B, SMCHS, Block B, Karachi or call at 021-34392159
Revocation/Cancellation of Form-6 (Provisional Certificate for Enlistment as manufacturer/importer) & Form-7(Provisional Certificate for Enlistment of products)
Decisions of 52nd Meeting of Medical Device Board (Deficiency letters Local/Import)
The Medical Device Board (MDB) of Drug Regulatory Authority of Pakistan in its 52nd meeting has deferred the following applications of registration of medical devices due to various deficiencies / shortcomings in the applications dossiers. These applicants are requested to furnish the requisite information / documentations as directed by the Medical Device Board. The detail is provided in the below attachment
Decisions of 51st Meeting of Medical Device Board (Deficiency letters Local/Import)
The Medical Device Board (MDB) of Drug Regulatory Authority of Pakistan in its 51st meeting has deferred the following applications of registration of medical devices due to various deficiencies / shortcomings in the applications dossiers. These applicants are requested to furnish the requisite information / documentations as directed by the Medical Device Board. The detail is provided in the below attachment.
Rapid Alert: Drug Product; Falsified Tablin 300mg Capsule identified in the market
Rapid Alert
Suspected Falsified Product
| DRAP Alert No | NoI/S/10-22-36 |
| Action Date | 24th November 2022 |
| Target Audience | 1. Regulatory Field Force 2. Pharmacists and Chemists at Distribution, Pharmacies and Medical Stores 3. Healthcare Professionals- Physicians, Pharmacists, and Nurses at hospitals, Clinics and Healthcare Institutions 4. General Public |
| Problem Statement | During the market surveillance activities in different areas of District Sheikhupura Punjab, Regulatory Field Force has identified the suspected sample for product and sent for analysis to laboratory. The Provincial Drugs Testing Laboratory, has declared the samples as “spurious”. The stated manufacturers on the label has informed that they have not manufactured this batch number of product. Product detail is as under:- |
Therapeutic Good Affected:-
| Sr | Product Name | Composition | Batch # | Manufactured by (as stated on label) |
|---|---|---|---|---|
| 1 | TABLIN 300mg Capsule | Pregabalin 300mg | Batch No. 699 | M/s Theramed Pharmaceuticals (Pvt) Ltd, Lahore. |
| Action Initiated | The Regulatory Field Force has been directed to increase the market surveillance and confiscate this batch of the product. All Pharmacists and chemists working at distributions and Pharmacies should immediately check the stock and stop supplying this product. The remaining stock should be quarantine immediately, and supplier(s) information should be provided to the Regulatory field force (DRAP, Provincial Health Departments and States) in order to ensure the removal of suspected products. |
| Advice for Healthcare Professionals | -DRAP requests increased vigilance within the supply chains of institutions/pharmacies/healthcare facilities likely to be affected by these batches of above-mentioned product. -Adverse reactions or quality problems experienced with the use of this product 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 | -Consumers should stop using this product and shall contact to their physician or healthcare provider if they have experienced any problems that may be related to taking or using this drug product, and report the incident to Drug Regulatory Authority of Pakistan / National Pharmacovigilance Centre. -All therapeutic goods must be obtained from the 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. |
Recall Alert: Drug Product; Ponstan Forte 500mg Tablets (Batch # 2050533) by M/s Pfizer Pakistan Ltd, Karachi.
Recall Alert
| DRAP Alert No | NoI/S/10-22-35 |
| Action Date | 30th November 2022 |
| 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 | Ponstan Forte 500mg Tablets, Active Ingredient(s): Mefenamic Acid Company: M/s. Pfizer Pakistan Ltd, Karachi Batch No. 2050533 Manufacturing Date: 09-2020 Expiry Date: 08-2025 |
| Problem / Issue | The Drug Testing Laboratory, Baluchistan has analyzed the sample of batch No. 2050533 of Ponstan Forte 500mg Tablets manufactured by M/s. Pfizer Pakistan Ltd Karachi, Pakistan and declared it as “Substandard” based on the analysis. |
| Action Initiated | -The company is directed to immediately recall the defected batch of product from the market. -All Pharmacists and chemists working at distributions and Pharmacies are required to immediately return the stock of above-mentioned batch of product to the supplier / importer / 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. |
Recall Alert: Drug Product; Diamicron 80mg Tablets (Batch#1740) by M/s. Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd Lahore.
Recall Alert
| DRAP Alert No | NoII/S/10-22-33 |
| Action Date | 23rd November 2022 |
| 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 | Diamicron 80mg Tablets, Active Ingredient(s): Gliclazide Company: M/s. Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd Lahore. Batch No. 1740 Manufacturing Date: 04-2022 Expiry Date: 04-2025 |
| Problem / Issue | Central Drug Laboratory, Karachi has analyzed the samples of Diamicron 80mg Tablets manufactured by M/s Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd Lahore and declared the batch No. 1740 as “substandard” based on the analysis report. |
| Action Initiated | -The company is directed to immediately recall the defected batch of product from the market. -All Pharmacists and chemists working at distributions and Pharmacies are required to immediately return the stock of above-mentioned batch of product to the supplier / importer / 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: Risk of Kidney Injury and Death due to Hydroxyethyl-Starch Solutions for Infusion.
Drug Safety Alert
Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan
| Date: | 29th of November, 2022 |
| Target Audience: | • Manufacturers and importers of hydroxyethyl-starch solutions for infusion. • Healthcare Professionals; and • Patients, consumers or caregivers. |
| Background: | The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicine Agency (EMA) on 11th February, 2022 recommended that the market authorization of hydroxyethyl-starch (HES) solutions for infusion should be suspended across the European Union. These solutions for infusion products are indicated as an addition to other treatments for plasma volume replacement following acute (sudden) blood loss. The safety of these solutions for infusion was reviewed in 2013, and a number of restrictions and measures to minimise the risk of kidney injury and death in certain patients (those critically ill, with burn injuries or with sepsis, a bacterial infection in the blood) were put in place at that time. Likewise, as a result of a third review conducted in 2018, the use of HES solutions for infusion was further restricted to only accredited hospitals, and healthcare professionals prescribing or administering the medicines had to be trained in their appropriate use. In addition, further warnings were introduced to remind healthcare professionals that these medicines must not be used in patients with sepsis or kidney impairment or in other vulnerable patients such as the critically ill in order to ensure these solutions for infusion were not used in patients who were at increased risk of harm. Market authorization holders of HES solutions for infusion were also requested to conduct a drug utilization study to check that the restrictions were adhered to in clinical practice. The PRAC of the EMA accordingly reviewed the results of the study, which show that HES solutions for infusion are still being used outside the recommendations included in the product information and concluded that the further restrictions introduced in 2018 have not sufficiently ensured that the medicines are used safely and that HES solutions were continually used in certain groups of patients in whom serious harm has been demonstrated. In view of the serious risks that certain patient populations were still exposed to, the PRAC recommended the suspension of the marketing authorizations for HES solutions for infusion in the European Union. Accordingly, the European Commission on 24th May, 2022 issued a legal decision confirming the suspension of the market authorization of HES solution for infusion. |
| Therapeutic Good(s) Affected: | Name: Hydroxyethyl-Starch solutions for infusion. These solutions for infusion products are indicated as an addition to other treatments for plasma volume replacement following acute (sudden) blood loss. |
| Action in Pakistan | Accordingly, the case of the risk of kidney injury and death due to hydroxyethyl-starch solutions for infusion was discussed in the 1st 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). The PRAEC-DRAP after detailed deliberation and discussion and as per Rule 10 (1) (h) (v) of Pharmacovigilance Rules, 2022 (reliance mechanism) decided to recommend to the Registration Board of the DRAP to suspend the registration of Hydroxyethyl-Starch (HES) solutions in Pakistan subject to the availability of alternative treatment options. |
| Advice for healthcare professionals: | Healthcare professionals are informed that the National Pharmacovigilance Centre, DRAP is working with the Registration Board and manufacturers/importers of hydroxyethyl-starch solutions for infusion to suspend the registration of these solutions in Pakistan. Therefore, healthcare professionals are reminded that there are alternative solutions for infusion available in the Pakistani market for the treatment of plasma volume replacement following acute (sudden) blood loss and the same must be considered as the treatment in these conditions. |
| Advice for patients: | Patients are informed that the National Pharmacovigilance Centre, DRAP is working with the Registration Board and manufacturers/importers of hydroxyethyl-starch solutions for infusion to suspend the registration of these solutions in Pakistan. Therefore, talk with your doctor before initiation of treatment with those solutions as alternative treatment options are available in the market. |
| 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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. European Medicine Agency update regarding hydroxyethyl-starch solutions for infusion recommended for suspension from the market. |
Drug Safety Alert: Risk of Major Congenital Malformations with Pregabalin
Drug Safety Alert
Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan
| Date: | 29th of November, 2022 |
| Target Audience: | • Manufacturers and importers of Pregabalin; • Healthcare Professionals; and • Patients, consumers or caregivers. |
| Background: | The Medicine and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom on 19th April, 2022 announced that the product information for pregabalin will be updated to include information from a new study which has suggested pregabalin may slightly increase the risk of major congenital malformations if used in pregnancy. The MHRA reviewed the results of a Nordic observational study that consisted of 2,700 pregnancies exposed to pregabalin in the first trimester, alongside a recent European review which had the same conclusions. The study showed a higher prevalence of major congenital malformations in the babies (live or stillborn) exposed to pregabalin in the first trimester of pregnancy compared with those not exposed to pregabalin or any other antiepileptic drug. The review concluded that pregabalin’s use during the first trimester of pregnancy may cause a slight increase in the risk of major congenital malformations in the unborn child. Furthermore, the Health Products Regulatory Authority (HPRA) of Ireland back in February 2022 also recommended that product information of Pregabalin along with other anti-epileptic drugs be updated based on the evidence of risks associated with in-utero exposure to these drugs. The product information of pregabalin continues to advise that effective contraception should be used during treatment and that use in pregnancy should be avoided unless it is necessary. |
| Therapeutic Good(s) Affected: | Name of Drug: Pregabalin Pregabalin is indicated for the treatment of peripheral and central neuropathic pain in adults, as adjunctive therapy in adults with partial seizures with or without secondary generalization, and for generalized anxiety disorder in adults. |
| Action in Pakistan | Accordingly, the case of the risk of major congenital malformations with Pregabalin was discussed in the 1st 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). The PRAEC after detailed deliberation and discussion decided as per Rule 10 (1) (h) (iv) and (vi) of Pharmacovigilance Rules, 2022 (reliance mechanism) to update prescribing information of Pregabalin to include information from a new study that pregabalin may slightly increase the risk of major congenital malformations if used in pregnancy and include advise on effective contraception during treatment in pregnancy. |
| Advice for healthcare professionals: | A new study has demonstrated that pregabalin may slightly increase the risk of major congenital malformations if used in first trimester of pregnancy. Therefore, healthcare professionals should provide counselling to the patients on potential risks to an unborn baby with pregabalin and also on the need to use effective contraception during the treatment. Healthcare professionals are also advised to continue to avoid the use of pregabalin during pregnancy unless clearly necessary and only if the benefit to the patient clearly outweigh the potential risk to the fetus. In case where the benefit outweighs the risk, and it is clearly necessary that pregabalin has to used during the pregnancy, then the lowest effective dose should be used. |
| Advice for patients: | Patients are advised to talk to their doctors before initiation of treatment with Pregabalin and discuss the benefit-risk of the medicine, particularly related to their case. Patients are also advised to talk with their healthcare professionals and use an appropriate contraception method during the treatment with Pregabalin to avoid pregnancy. |
| 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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. Pregabalin (Lyrica): findings of safety study on risks during pregnancy of MHRA. |