LCQ5: Quality of pharmaceutical products
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Question:
In December 2014, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use promulgated a Guideline for Elemental Impurities (the Guideline), which provides for qualitative and quantitative limits on metal impurities in drug products and ingredients. It has been reported that a drug manufacturer which produced a potassium supplement named "Slow K" notified the Department of Health (DH) in December last year that taking a high dose of that drug by patients might result in their intake of lead exceeding the standards stipulated in the Guideline. The drug manufacturer concurrently informed the Hospital Authority (HA) of its decision to cease the production of that drug product for the aforesaid reason. However, due to an insufficient supply of alternative drugs, pharmacies of public hospitals and outpatient clinics continued to dispense Slow K to patients without telling them the associated risks. Only after the aforesaid incident had been disclosed in newspapers in mid-March this year did those pharmacies switch to dispense alternative drugs. In this connection, will the Government inform this Council:
(1) whether drug products applying for registration in Hong Kong are currently required to meet certain metal impurities standards; if so, of the details, including the international organisations or overseas drug regulatory authorities which promulgated the standards concerned; if not, the reasons for that and whether relevant standards will be set;
(2) whether the authorities have reviewed if the existing registered drug products meet the metal impurities standards stipulated in the Guideline; if they have, of the outcome; if not, the reasons for that;
(3) how the authorities handle the following situations: where a registered drug product is found (i) to contain metal impurities of levels exceeding the relevant standards promulgated in the Guideline or by other international organisations or overseas drug regulatory authorities, or (ii) to be no longer suitable for prescribing to patients;
(4) how DH and HA handle the unexpired Slow K in stock;
(5) whether it knows if HA will recall the Slow K which has been dispensed to its patients, and whether the authorities will deregister that drug product; if HA will, of the details; if not, the reasons for that; and
(6) whether it knows if HA will arrange blood tests for those patients who have taken Slow K for a long period of time to ascertain if their blood lead levels are normal; if HA will, of the details; if not, the reasons for that?
Reply:
President,
In consultation with the Department of Health (DH) and the Hospital Authority (HA), a consolidated reply to the six parts of the question is as follows:
(1) to (3) Under the Pharmacy and Poisons Ordinance (Cap. 138), pharmaceutical products should meet the criteria of safety, efficacy and quality and be registered with an independent statutory body, the Pharmacy and Poisons Board (PPB) before they can be sold in Hong Kong. The DH has been tasked to provide professional advice and executive support to the PPB. The registration certificate of a pharmaceutical product is valid for 5 years and renewal application should be submitted to the PPB before it expires.
Application for registration of pharmaceutical products in Hong Kong must be accompanied by the required supporting documents stipulated by PPB in the "Guidance Notes on Registration of Pharmaceutical Products/Substances". They include the master formula and specification of the product (which generally adopt the pharmacopeial standards). The required documents and evaluation standards are set mainly having regard to the drug registration recommendations of advanced drug regulatory authorities and reputable international organisations (for example the World Health Organization).
The registration of pharmaceutical products can be divided into two main categories including new chemical entities and non-new chemical entities (generic products). Currently, Hong Kong adopts a secondary review approach to the registration of pharmaceutical product. For new chemical entities, the PPB will assess the safety, efficacy and quality based on the evaluation results conducted by the drug regulatory authorities of reference countries (there are now 32 reference countries whose drug regulatory authorities fully implement the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines). For generic products, their safety and efficacy should be supported by reputable literature references. Regarding quality, applicants of both new chemical entities and generic products must provide evidence that the manufacturers of pharmaceutical products have complied with the Pharmaceutical Inspection Co-operation Scheme (PIC/S) Good Manufacturing Practice (GMP) standards, and the specification of product should comply with the requirements of relevant pharmacopoeia or quality standards.
ICH guidelines are of top science level and their implementation requires advance technology. According to the report issued by the World Health Organization in 2002 on the impact of implementation of ICH Guidelines among non-ICH countries, it mentions among others the high costs related to full implementation of the guidelines by the industry, which may lead to withdrawal of the marketed drugs and may adversely affect public health. As for the domestic drug market in Hong Kong, 80% of the pharmaceutical products are imported. Together with products manufactured locally, about 60% of pharmaceutical products are manufactured in non-ICH countries/regions. Currently, the PPB does not require the compliance of ICH guidelines as registration requirement.
Nevertheless, having regard to the inclusion of elemental impurities (including lead level) as quality standard by the British and US Pharmacopoeias in accordance with the ICH requirement, the PPB will consider and discuss whether such standard should be included as registration requirement. The trade will be consulted in the process.
(4) and (5) Regarding the incident of modified release potassium chloride tablet (Slow K) exceeding ICH lead level limit, the DH considered that there is no evidence showing the product on the market does not comply with its registered product specification or the pharmacopoeial standards applicable to the products at the time of manufacture, and that there is no need for recalling the product. However, having considered public and patient concerns on the quality of the product, the clinic dispensaries under the DH has stopped dispensing Slow K by the end of March upon the availability of alternative source of supply. The remaining undispensed Slow K will be arranged for disposal as chemical waste in accordance with the relevant regulation under the Waste Disposal Ordinance (Cap. 354).
The supply of potassium chloride tablets from the new drug suppliers has stabilised since end of March 2018. The HA has completely suspended using the original tablets and the remaining stock will be disposed of according to established procedure. Currently, the HA does not recall the potassium chloride tablets dispensed to patients. The HA will take appropriate follow-up actions in accordance with the guidelines of the DH.
On the other hand, the DH has closely monitored the relevant drug safety information announced by other overseas drug regulatory authorities. So far there is no similar incident related to other registered pharmaceutical products. If any pharmaceutical product available in Hong Kong has impact on public health, the DH will take immediate actions as deemed appropriate.
(6) The HA has followed up on all patients taking high-dose potassium chloride tablets and arranged blood tests for individual patients. No abnormal results have been observed so far.
Ends/Wednesday, April 25, 2018
Issued at HKT 15:36
Issued at HKT 15:36
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