Drug Regulation Flashcards
HSA
- Formed on 1 April 2001 as a statutory board of the Ministry of Health
- Key regulatory functions
I. To regulate health products (license required)
§ Quality, safety and efficacy
II. To serve the administration of justice
§ Forensic medicines, forensic science and analytical chemistry testing
III. To secure the nation’s blood supply
§ Safe and adequate blood supply for Singapore public
Legislative Framework in Singapore
- Misuse of Drug Acts
- Health Products Acts
I. Medicinal products/pharmaceutical drugs are called “therapeutic
products” under the Health Products Act - Medicines Act / Medicines (Advertisement and Sale) Act
- Sale of Drugs Act
- Poison Act
- Tobacco (Control of Advertisement and Sale) Act
License not needed
- Health supplements
- Cosmetics products
- Traditional medicines(Indian and Malay)
License needed
- Therapeutics Products
- Medical devices
- Chinese proprietary medicines
- Tobacco products
Therapeutic Producs
- Therapeutic products are:
I. drugs or pharmaceuticals.
II. healthcare products for therapeutic, preventive, palliative, or diagnostic purposes.
III. Required to be registered and licensed by HSA before being imported, manufactured or sold in Singapore. - Are drugs used in clinical trials being regulated?
I. Yes! Must be in concordance with HSA regulations.
II. It is mandatory for drug companies to report all serious adverse
effects.
Drugs Regulated In Singapore
Drugs regulated in Singapore
* New chemical entity
* New molecular entity
* Generic drug
* Biosimilar drug
-> Foreign and local sources
-> What are the differences between generic and biosimilar drugs?
Drugs not subjected to licensing by HSA
Drugs not subjected to licensing by HSA
* Cosmetic products and health supplements.
* Are not subject to approvals and licensing by the HSA for their
importation, manufacture, and sales.
* Importers, manufacturers, or wholesalers must ensure that their products are not harmful or unsafe.
* Addition of prohibited medicinal ingredients are prohibited.
* Strict labeling standards:
I. In English and legible.
II. conspicuously displayed on the product at the point of sale
Liceses for Therapeutic Products
- Licenses for therapeutic products to be registered by HSA.
I. Therapeutic Product Manufacturer’s License (TPML)
II. Form A Poisons License (FAPL)
III. Therapeutic Products Importer’s License (TPIL)
IV. Therapeutic Products Wholesaler’s License (TPWL)
V. Retail Pharmacy License - How about clinical trial drugs?
- Clinical trial drugs do not require TPIL and TPWL as clinical research materials.
Risk-calibrated evaluation FDA
Risk-calibrated evaluation of new drugs by FDA
* In 2009, FDA initiated benefit-risk framework for human drug review by CDER (Center for Drug Evaluation and Research).
* Two main goals
* Better communication regarding regulatory decision.
* Ensure that the ”big picture” is maintained throughout the review process.
* A structured, qualitative approach is favorable:
* More rigorously communicates the basis for decision
* Flexible to accommodate supporting qualitative analyses.
Risk-calibrated evaluation HSA
full - no prior approval worldwide, full review of quality and clinical data
abridged - at least one prior approval, full review of quality data, abbreviated review of clinical data
verification - at least 2 RA approvals(NDA)/1RA approval(GDA), review based on RA assessment report(quality and clinical), review of stability data as per ASEAN requirements(region-specific)
Risk Evaluation Areas
Benefit-risk assessment for new drugs
* Therapeutic efficacy
- Magnitude of effect size
* Convenience
* Study endpoint and patient outcome
- Overall population or
- Specific subset of patients
* Adverse drug reactions
* Risk factors are different across all patients
- age,
- kidney function,
- liver function,
- complications with other medicines,
- concomitant disease etc
Challenges of RBA
Risk-based approach is a complicated process..
* Of the 22 novel drugs approved by CDER in 2016:
* 6 were completed as priority review.
* 8 were first-in-class.
* 9 were approved for rare diseases.
* 19 were approved first in the U.S.
* 21 were approved in their first review cycle.
Quality
Quality of new drugs
* Drug substance (active ingredients) and drug product (finished products) are regulated for:
I. Manufacturing process
II. Control of materials and their intermediates
III. Process validation
IV. Manufacturing process development
V. Specifications
VI. Container closure system
VII. Stability
Manufacturing process and controls ensure consistent manufacturing of good quality products
Non-clinical safety of new drugs
Non-clinical safety of new drugs
* Pharmacology and pharmacokinetics
* Toxicology
I. Single-dose and repeat-dose toxicity
II. Genotoxicity
III. Carcinogenicity
IV. Reproductive and developmental toxicity
V. Local tolerance
Establish safety & toxicity before proceeding to human studies.
Clinical efficacy and safety of new drugs
Clinical efficacy and safety of new drugs
* Biopharmaceutic studies: pharmacokinetics and pharmacodynamics
* Study design to evaluate clinical efficacy and safety:
I. Inclusion/exclusion criteria
II. Treatment regime
III. Efficacy endpoints
IV. Statistical method
V. Study population, demographics and baseline characteristics
VI. Efficacy analysis
VII. Safety analysis
Provides confirmatory efficacy & safety data for benefit vs risk assessment of the drug
Enabling rapid response to emergency
- The regulatory framework for new drug registration (and market authorization) caters primarily for “peace time” approval.
- R&D takes time
- Conclusive evidence is needed on quality, safety and efficacy.
- Pandemic Special Access Route (PSAR)
- Interim authorization based on interim evidence to expedite access for emergency therapeutic products
- Not a marketing authorization for commercialization and supply is to be directed by the Government
Bridging pre- and post-market
At the point of marketing approval, information on safety & efficacy based primarily on clinical trial data in limited population under controlled clinical setting
On-going reassessment is needed to monitor emerging safety & efficacy data to optimize benefit-risk of the drug and modify/update the product label as necessary
