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Introduction
1. The Health Products Act (HPA) (Cap. 122D) was enacted in 2007 with the objective of consolidating and streamlining the different medicines control laws into a single law in phases to cover a range of health products. Currently, only medical devices (MD) and cosmetic products are regulated under the HPA, and the rest of the medicinal products are still regulated under the Medicines Act (MA) (Cap. 176) and Poisons Act (PA) (Cap. 234).
2. The transfer of pharmaceutical products from the MA and PA to the HPA is one of the Health Sciences Authority’s (HSA) on-going initiatives to consolidate all regulatory controls into a single piece of legislation. The aim is to provide clarity with a single law to refer to, and the regulatory controls will be stratified based on the risk profiles of the products. Pharmaceutical products, conventionally termed as chemical and biologic drugs, will be introduced as a new category of health products in the First Schedule of the HPA using the term “therapeutic products” (TP). Thereafter, the existing controls for pharmaceutical products under the MA and PA will be dis-applied.
3. The new Regulations under the HPA will cater to different operational and business models in the rapidly evolving pharmaceutical landscape, while remaining relevant and adequate to safeguard public health and to facilitate timely access to TP.
4. HSA held two public consultation exercises on the proposed plans to transfer the existing regulatory controls of pharmaceutical products from the MA and PA to the HPA (please refer to Table 1 for the draft Regulations that were opened for consultation for each exercise). The first consultation, held from 27 October 2014 to 23 November 2014, covered controls on advertisements for TP and retail pharmacy licensing. The second consultation, held from 15 December 2015 to 15 January 2016, covered the proposed definition for “therapeutic product”, its licensing regime and clinical trial controls. Face-to-face briefings were also conducted with representatives from the industry, healthcare professionals and healthcare institutions.
Table 1: Public Consultations on the Draft Regulations under the HPA
5. HSA received a total of 431 responses from 132 respondents over the two consultation periods. A summary of the respondent categories and number of feedback by specific Regulations is presented below in Table 2 and Table 3.
Table 2: Category of Respondents
Table 3: Breakdown of Feedback by Type of Regulations
6. The majority of feedback received involved operational and technical enquiries on the requirements and provisions of the draft Regulations, including enquiries about the Form A Poisons Licence, notifications for Import for Re-export upon the transfer of TP controls, and specific licensing requirements for different operating scenarios. HSA will provide the relevant guidance documents and frequently-asked-questions (FAQs) on our website prior to the implementation of the transfer of regulatory controls to address these concerns.
7. There were also specific suggestions concerning various aspects of the proposed controls. HSA has noted these points, and will factor them into the final legislation and implementation.
8. The main feedback received in the two consultations and our responses to the suggestions are detailed in the following sections.
Health Products (Amendments to the First Schedule) Order
9. Two respondents requested for clarity on the definition of TP. The proposed description for “therapeutic products” is a function-based definition, which remains similar to the definition of “medicinal products” in the MA. It now includes an additional criterion defining the form to be either a chemical or biologic drug, which is the conventional form of “western pharmaceutical products”, and this will be transferred to the Health Products (TP) Regulations. This will provide greater clarity on the types of products that will be regulated after the transition.
Health Products (TP) Regulations
Transfer of unregistered products between affiliated companies for purposes of export
10. HSA received three enquiries on how the Regulations would apply or impact companies if unregistered TP were transferred from one company to another affiliated company due to internal operations and arrangements for purposes of export.
11. HSA’s regulatory focus is to reduce the risk of such unregistered TP being diverted into the local market. Companies must ensure that the unregistered TP are re-exported and not diverted to the local market. The companies must hold the relevant licences e.g. Importer’s Licence (IL) and Wholesaler’s Licence (WL). They must also ensure that the unregistered products are not controlled drugs or psychotropic substances because these will require a licence from HSA, even if they are imported for re-export. HSA will conduct checks on companies to ensure that they comply with requirements.
Companies importing and wholesaling unregistered TP for patients’ use only
12. There were four enquiries regarding the regulatory requirements needed for the supply of unregistered TP for patients’ use.
13. Under the proposed TP Regulations, companies involved in the import and wholesale of unregistered TP for patients’ use will now need to apply for an IL and WL, as well as comply with Good Distribution Practice (GDP) requirements. GDP is an essential requirement to assure quality and safety of TP, through compliance with good record keeping, handling, storage and distribution standards. To assist companies in the transition, those importing and wholesaling unregistered TP for patients’ use only will be given a grace period to level up to the GDP requirements, and their IL and WL fees for these activities will only be imposed after that period.
Compounding of TP
14. A number of respondents enquired and provided feedback on issues related to the compounding of TP, which included: scenarios where compounding is allowed; whether re-packing requires a doctor’s prescription or written instruction; and the establishment of expiry dates for compounded products.
15. HSA has taken these feedback into consideration and will be making the following changes to the TP Regulations:
a. Pharmacy-only (P) and general sale list (GSL) TP may be compounded without a written doctor’s instruction as they are generally lower-risk products.
b. Re-packing conducted at private hospitals, medical clinics or retail pharmacies will be allowed without the need for a doctor’s written instruction.
16. The establishment of expiry dates for compounded products, including re-packed products where the immediate container has been changed, should be in accordance with specified publications, namely the British Pharmacopoeia, the European Pharmacopoeia, the United States Pharmacopoeia and the National Formulary. If the assigned expiry date of compounded TP is beyond the general recommended durations of the specified publications, objective documented evidence from stability studies must be available.
17. Reconstitution or dilution performed in accordance with the directions for use on the TP’s label will not be considered as manufacturing or compounding.
Responsible Person
18. Some respondents sought clarification on the Responsible Person (RP) to be named in the IL and WL. HSA has clarified that under the TP Regulations, the company (or licensee) must designate one or more competent personnel, known as the Responsible Person (RP), to be in charge of matters related to GDP compliance. The RP is required to be named in the IL and WL, and must be employed on a full-time or part-time basis by the company to carry out the tasks/duties related to GDP compliance.
19. Further details and guidelines on the duties of responsible persons named in the IL and WL will be made available on HSA’s website.
Labelling of name and address of supplier on TP
20. Under the proposed TP Regulations, the name and address of the supplier shall be labelled on the Prescription-Only medicines (POM) and P medicines supplied. This requirement was intended to ensure the traceability of the TP in the event of a recall. HSA considered the feedback from the industry that companies may face logistical challenges and a higher financial burden in complying with this requirement for each wholesale supply.
21. Having considered the feedback and reviewed the process, HSA has assessed that the records kept by the suppliers for wholesale supply will suffice to meet HSA’s requirement for traceability of the TP. HSA will therefore remove this requirement from the TP Regulations.
Supply of TP for veterinary use
22. Under the proposed TP Regulations, TP are health products that are supplied solely for use in humans. The supply of TP at retail pharmacies and by wholesalers for use in animals comes under the purview of the Agri-Food & Veterinary Authority of Singapore (AVA). If a TP has been supplied for use in animals, the supply and the conditions pertaining to such supply needs to fulfil the requirements stipulated by AVA.
23. HSA-licensed retail pharmacies and wholesalers may continue to supply TP for animal use based on valid veterinary prescriptions and signed (purchase) orders from AVA-licensed veterinarians, veterinary clinics, feedmills, farms and AVA-registered wholesalers which are supplying TP solely for veterinary use. A list of all businesses authorised to purchase TP from HSA-licensed retail pharmacies and wholesalers will be provided by AVA for reference.
Health Products (Clinical Trials) Regulations; Health Products (Therapeutic Products as Clinical Research Material) Regulations; Health Products (Medical Devices) (Amendment) Regulations
Definition of observational trial
24. Two Institutional Review Boards (IRBs) had submitted feedback to suggest removing the criterion of “no additional diagnostic or monitoring procedures, other than those ordinarily required for the particular treatment in clinical practice” from the definition of observational trials. HSA has reviewed this, and agrees to remove this criterion to ensure a more risk-proportionate regulatory framework that focuses on the risk of the TP used in the trial.
25. However, as an additional safeguard, all serious adverse drug reactions arising from the use of TP in observational trials will still be subject to safety reporting requirements by HSA, so that any untoward adverse effects will be detected in a timely manner through such surveillance.
Criteria for clinical trials notification (CTN)
26. There was feedback for HSA to consider allowing unregistered therapeutic products with extensive experience of use as standard of care to also qualify for the CTN route.
27. While HSA acknowledges that some unregistered drugs may be safe due to a history of safe use, the registration status of a therapeutic product serves as an objective proxy for risk-classification of a trial to qualify for notification route. Hence it will be retained as a requirement.
Criteria for Principal Investigator
28. There was a suggestion for HSA to consider allowing registered pharmacists to be Principal Investigators in clinical trials involving solely Pharmacy-only medicines, as pharmacists are trained in the use of such medicines.
29. HSA will retain the current requirements as medical oversight for the protection and safety of clinical trial participants is required. However, HSA acknowledges the evolving role of pharmacists and other allied healthcare professionals in patient care, and will continue to review the policy on this matter in consultation with stakeholders and the Ministry of Health.
Conditions relating to clinical trial insurance
30. A few comments on the subject of insurance for clinical trials, including seeking clarification on the terms and exclusions for insurance coverage and indemnity by the Sponsor for the approved or notified clinical trial, were received.
31. HSA has reviewed the feedback and will require sponsors to maintain insurance as is currently required under Good Clinical Practice (SG-GCP 5.8.1). The insurance will continue to be reviewed by the institutions, as is currently practised, for the purpose of the Clinical Trial Agreement.
Written certification for subject enrolment in emergency situation
32. The proposed Regulations states that the Principal Investigator must give written certification prior to enrolment of a subject in an emergency trial. There was feedback seeking clarification on whether the Co-Investigator may also give the written certification, as the Principal Investigator may not always be available.
33. HSA acknowledges and assesses that the Co-Investigator, who is also a specialist, should be sufficiently qualified to make the written certification. While the Principal Investigator will still be responsible for ensuring that the trial is conducted in accordance with the Regulations, HSA will update the Regulations to allow the Co-Investigator to perform the certification prior to subject recruitment, with the safeguard above.
Health Products (Advertisements for Therapeutic Products) Regulations
Sales promotions including multiple pack discounts
34. Under the proposed Regulations, any discount or price reduction conditional upon a minimum quantity of the TP purchased is to be prohibited, as this may induce unnecessary consumption of the TP. Respondents, however, shared that multiple packs promotion is commonly practised, and can provide value to patients with certain chronic conditions. They also shared that the purchase and dispensing of P medicines will still continue under the supervision of a pharmacist who acts as an additional layer of control for these higher-risk products.
35. HSA has considered the feedback, and assessed that multiple packs can benefit consumers who require long-term medication and help to lower healthcare expenditure for them. HSA will therefore continue to allow multiple pack promotions for P and GSL medicines. HSA will however advise companies to ensure that sales promotions do not induce or encourage inappropriate or excessive consumption of the TP as prescribed in the Regulations. Additional safeguards will include the prohibition of direct-to-consumer advertisements of POM, and the prohibition of banding of TP with medicinal / health products.
Controls for corporate and e-commerce websites
36. A few respondents sought clarification from HSA on whether the prescribed requirements under the Regulations apply to corporate websites of registrants and licensees of TP, as well as microsites and websites belonging to third parties such as related company entities, retailers, and e-commerce portals.
37. HSA has clarified that Internet advertisements have to comply with the requirements as prescribed in the Regulations, including the prohibition of direct-to consumer advertisements of POM and the prohibition of direct-to consumer advertisements making reference to the specified diseases and medical conditions listed in the Regulations. These include blindness, cancer, cataract, conception and pregnancy, deafness, diabetes, drug addiction, epilepsy or fits, frigidity, hypertension, impotency, infertility, insanity, kidney diseases, leprosy, menstrual disorders, paralysis, sexual function and tuberculosis. However, local corporate websites operated by licensees/registrants of the TP will be allowed to feature factual information about their own products, including information on POM and diseases or conditions listed in the Regulations. Product launch events that are not accessible to the public and press releases may also carry factual information, similar to that of the corporate websites. Discussion forums on the corporate websites will not be allowed.
38. Advertisements of TP published on platforms such as microsites and e-commerce websites which are targeted at consumers will remain subject to medical advertisement controls.
Removal/amendment of certain prescribed principles for advertisement
39. There were suggestions to remove or amend certain prescribed principles for advertisement, such as comparative advertising, use of images to show consequences of non-treatment, advertising to minors and generic comparison claims.
40. HSA noted the suggestions but will retain the prescribed principles for advertisements to protect consumers from being misled.
Health Products (Licensing of Retail Pharmacies) Regulations
41. There was a suggestion that the pharmacist-in-charge of a retail pharmacy must be a registered pharmacist and possess a valid and active practising certificate. This feedback has been accepted and will be incorporated into the legislation.
42. HSA has also noted the feedback on licence requirements, the validity of overseas prescriptions, inspection criteria for a licensed pharmacy, and the services/activities allowed to be carried out by a retail pharmacy. HSA will provide clarifications on these areas through the various guidance documents and FAQs that will be shared prior to implementation.
Conclusion
43. HSA would like to thank all individuals and organisations for their valuable feedback during these two public consultation exercises.
44. Announcements and email alerts will be sent to affected stakeholders prior to and upon the implementation of the transfer of regulatory controls from the MA and PA to the HPA.
HEALTH PRODUCTS REGULATION GROUP
HEALTH SCIENCES AUTHORITY
1 JULY 2016
