Medicines quality and Losartan recall

Name and Constituency of Member of Parliament
Ms Irene Quay Siew Ching
Nominated MP

Question No. 2777
To ask the Minister for Health (a) how rigorous is medication tested by the Health Sciences Authority before the drugs enter Singapore; (b) whether the testing is in line with international testing standards; (c) whether there are public concerns with generic use of medications in Singapore; and (d) what are the steps and considerations taken by the Ministry compared to other countries' handling of the same worldwide concern, particularly with the Losartan recall.

Answer
1    The Health Sciences Authority (HSA) sets stringent standards on the quality and safety of medicines sold in Singapore. Before being approved for sale, the medicines are evaluated to ensure that they meet the required international standards of quality, safety and efficacy. HSA conducts in-depth technical assessments of the scientific data from clinical studies, as well as the manufacturing and quality control processes. In addition, HSA checks that the manufacturers conform to international standards of Good Manufacturing Practice.

2    After approval, HSA conducts post-market surveillance which includes monitoring of global developments and risk-based product sampling and testing for compliance to quality and safety specifications. Products found to be deficient in quality will be withdrawn from the market. Manufacturers are also required to test all batches of medicines to be sold in Singapore, including the levels of specific impurities, to ensure that they comply with stipulated standards.

3    Generic medicines are subject to the same strict regime of regulatory controls to ensure their safety, efficacy and quality.

4    The standards, checks and processes adopted by HSA are similar to those adopted by regulatory counterparts in other jurisdictions such as Australia, Canada, Europe, Japan and the United States. HSA’s Pharmaceutical Laboratory is also accredited to international standards, such as the International Organization for Standardization/International Electrotechnical Commission 17025 standard for testing laboratories. It is also a World Health Organisation Collaborating Centre for Medicines Quality Assurance.

5    On 28 March 2019, HSA recalled three brands of medicines which belong to the angiotensin receptor blocker (ARB) class of blood pressure medication and contain the ingredient losartan. Following the recall of several losartan medicines in US due to the presence of a nitrosamine impurity, N-nitroso-N-methyl-4-aminobutyric acid (NMBA), HSA tested the suspected losartan medicines and they were found to contain trace amounts of NMBA which are above the acceptable limit.

6    The routine tests required of the manufacturers are based on known impurities that may be generated during the manufacturing process, as it is not practical to exhaustively test for all types of impurities. In the case of the recalled losartan medicines, testing for nitrosamines like NMBA was not previously part of the testing parameters of ARB medicines as NMBA was not expected to be generated in the manufacturing process. This approach is similar to that adopted in other countries including the US, Canada and the European Union.

7    As the short term risk of taking the medicine was low, the advisory to affected patients was to continue taking their medicines until they are provided with suitable alternatives. Sudden stopping of their medication could pose greater and more immediate risk to patients’ health.

8   Meanwhile, HSA and our public healthcare family worked together to reach out to affected patients to facilitate a switch to alternative medicines. HSA tested all locally marketed ARB medicines to ensure that these alternatives do not contain NMBA. Public healthcare institutions then scheduled appointments for affected patients to switch to alternative medicines. The institutions also deployed additional staff to operate the hotlines for patient queries and set up service touchpoints to help patients switch their medicines. These actions went beyond what most other countries had done.

9    As of 28 Apr, we have helped more than half of the affected patients switch to alternative medicines. For all patients whose appointments are on or after 1 July, public healthcare institutions have already reached out to all of them to offer earlier appointments. We are on schedule to complete the exercise by end June. Since the recall, HSA has also been working with suppliers and international regulatory agencies to determine the cause of contamination, and to formulate measures to eliminate the nitrosamines in the medium to longer term. HSA will continue to monitor the quality and safety of these medicines to safeguard public health.