Overview of Drug Registration in Singapore Flashcards
1) What is HSA and its role?
Key regulatory functions:
- To regulate health products: Quality, safety and efficacy
- To serve the administration of justice: Forensic medicines, forensic science and analytical chemistry testing
- To secure the nation’s blood supply: Safe and adequate blood supply for Singapore public
2) What are the laws regulating pharmaceuticals in Singapore?
- Health products act: Health products (therapeutic products) regulation
- Misuse of drugs regulation
3) What is the product lifecycle approach?
(emerging areas)
- Product begins from scientific and technological developments
- eg. 3D printing (pre-market) - New drug undergoes pre market benefit-risk assessment (quality, efficacy, safety)
- drug registration
- GMP/GDP standards
- special access scheme - Drug undergoes marketing approval (post-market)
- Increasing knowledge
- Post market variation
- eg. New indication, change in manufacturing site, reclassification - On-going benefit risk assessment (pharmacovigilance)
- safety monitoring and risk benefit assessments of marketed health products
- risk communication with healthcare professionals and consumers
- product quality surveillance
- routine audits of dealers for GDP and GMP compliance - If there are safety issues, lack of efficacy, poor quality, removal of product
4) What are the requirements for drug registration in Singapore?
For foreign source:
- Undergo drug registration and obtain importer’s licence for importing drug
- Obtain wholesaler’s licence
- Obtain retail pharmacy licence
For local source:
- Obtain manufacturer’s licence and undergo drug registration
- Obtain wholesaler’s licence
- Obtain retail pharmacy licence
5) What are the different approaches to drug evaluation?
Abridged (1987):
-approved by 1 drug regulatory agency
full quality and abridged clinical; internal and external evaluation
-180 days
Full (1988):
- no prior approval by any drug regulatory agency
- full quality, non-clinical and clinical; internal and external evaluation
- 270 days
Verification (2003):
- approved by 2 reference agencies
- reference agency assessment report; internal evaluation only
- 60 days
6) What is the current approach to drug evaluation?
Risk based approach:
- Depth of evaluation calibrated according to prior approvals
- Multiple evaluation routes with different turnaround times allowing flexibility
- In-house capabilities complemented by external experts and advisory committee (Medicines Advisory Committee)
- Reference agencies: FDA, EMA, MHRA, TGA, Health Canada
7) What quality control information needs to to be submitted to HSA during drug registration
Manufacturing process and process controls;
control of material,
intermediates;
process validation;
manufacturing process development;
specifications;
container closure system;
stability (manufacturing process and controls ensure good quality product manufactured consistently)
8) What are the ongoing non-clinical tests required by HSA during drug registration? What is the importance of this information?
Pharmacology,
pharmacokinetics,
toxicology (single and repeat dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, local tolerance)
(establish safety and toxicity before proceeding to human studies. Provides information on potential safety signals)
9) What information about clinical efficacy and safety needs to be submitted to HSA during drug registration? What is the purpose of these information?
- Biopharmaceutic studies, PK/PD studies
- Clinical efficacy and safety studies: (mostly phase 1/2/3)
- study design:
- inclusion/exclusion criteria;
- treatment;
- efficacy endpoints;
- statistical method;
- study population,
- demographics and baseline characteristics;
- efficacy analysis;
- safety analysis
(provides confirmatory effect and safety data for benefit vs risk assessment of the drug)
10) How is risk-benefit assessment carried out for new drugs during drug registration?
- Study the efficacy vs safety profile via:
- magnitude of clinical benefit
- disease profile and prognosis
- adverse event profile
- local factors eg. Disease epidemiology, patient population - Decide if risks can be mitigated
11) What are the studies required for generics and biosimilars?
- Generics (conceptually exact copy of the innovator chemical drug):
- They need to evaluate the quality development.
- conduct bioequivalence studies to compare safety, efficacy and Pk parameters between the 2 drugs - Biosimilars (follow-on copies of the innovator biologic drug):
Need to show structural and functional comparability
need to conduct phase III clinical studies to compare the clinical effects of drugs vs innovator
12) How is post marketing monitoring carried out?
It is an on-going re-assessment of emerging safety & efficacy data to optimize benefit-risk of the drug and modify/update the product label as necessary.
- Risk management plan
–Measures to mitigate any potential risk associated with the use of a drug
–Physician education materials, patient medication guide –Active surveillance programmes (incl. targeted safety signal detection), restricted access scheme, registries, post-authorization clinical studies etc
- Other post-market surveillance activities
–ADR reporting (physicians who observe AE’s when prescribing drugs are to report it to HSA)
–Dissemination of safety information to healthcare professionals (e.g. Dear Healthcare Professional Letter)
–Product recall
13) How is transparency and predictability ensured?
- Publishing information on website:
- regulatory documents: submission requirements, guidance documents, checklists
- legislation
- processing timelines for drug applications -approvals of new drug and new indications -product labels - Communication with applicants:
- clarification of data during evaluation
- basis of regulatory decision (rejection of drug application) - Stakeholders engagement:
- industry dialogue and consultation prior to implementation of new regulations or regulatory requirments
