1
Q
Post Market surveillance relation to QMS
A
Post Market Surveillance is a subset of quality management system
2
Q
Post Market Period
A
User starts using to end-of-life disposal
3
Q
After-sales obligations
A
- Record keeping of supply
- Monitoring device’s clinical performance
- Identifying and correction action of any problems
4
Q
Effective post market surveillance
A
monitors performance of device under actual usage conditions to ensure public and patient safety
5
Q
Why is post market control important
A
ongoing safety and performance monitoring is important to ensure patient and public safety after device is released on the market
- inherent risk throughout the medical device life cycle, even for low risks ones,
- limitation of pre-market registration controls, and to
- enable timely intervention to safeguard public health.
6
Q
Responsibility of product risk management
A
lies in management
7
Q
What is post market surveillance
A
system providing continuous feedback about a device on the market to maintain high standard of product safety and quality
feedback is gathered via collection of processes and activities used to monitor the performance of a medical device after being released on the market
regulatory requirement in EU and ASEAN
8
Q
Proactive activities
A
- Customer surveys
- Post approval clinical studies
- Expert user focus groups
- Implant registries
9
Q
Reactive activities
A
- Customer complains
- Maintenance service reports
- Detection of manufacturing issues
- Vigilance (EA & FSCA)
10
Q
Post-market alert system requirements
A
- Distribution records
- Complaint records
- Adverse events (AE) reporting criteria and reporting format
- Field safety corrective action (FSCA) reporting format
11
Q
Definition of adverse events
A
By GHTF: malfunction or deterioration in characteristics or performance of a supplied medical device or use error, which has, or could have caused/ contributed to death/ injury of the patient or others
12
Q
objective of AE reporting and subsequent evaluations
A
improve protection of the health and safety of patients, users and others by disseminating information to reduce the likelihood of/ prevent repetition of AEs, or alleviate consequences of such repetition
13
Q
AE of IVD
A
consequence of a medical decision/ action taken/ not taken, on the basis of result(s) provided by the IVD medical device
14
Q
FSCA includes
A
- return of a medical device to the product owner or its representative which is recall
- Modification – which will be elaborated in the next slide
- Device exchange
- Destruct – it could be disposed at user’s end, product owner not collecting it back
- Advice given by product owner regarding the use of the device
15
Q
FSCA device modification may include
A
- Retrofit in accordance with the product owner’s modification or design change
- Permanent or temporary changes to the labelling or instructions for use
- Software upgrades including those carried out by remote access
- Modification to the clinical management of patients to address a risk of serious injury ordeath related specifically to the characteristics of the device
16
Q
Why is FSCA important
A
required when manufacturer of the medical device has to take action (including recall of the device) to eliminate/ reduce the risk of identified hazards
17
Q
Product recall
A
action taken by product owner to remove / retrieve the health product from the market
Product may be:
- hazardous to health
- unable to conform to any claim made by its product owner relating to its quality, safety or efficacy
18
Q
Who can initiate FSCA
A
- Product Owner
- Regulatory Agency
19
Q
HSA regulation
A
Health Product Act (HPA): regulate manufacture, import, supply, presentation and advertisement of all health products
Health Products (Medical Devices) Regulations 2010: covers control of medical devices only
20
Q
Medical Device Regulatory Framework
A
Legal Framework:
- Premarket registration
- Post-market
- Medical device establishment
21
Q
Pre-market registration
A
- Medical device definition
- Medical device classification
- Medical device registration Z(Class A exempted)
22
Q
Post-market
A
- Adverse events (AE) report criteria
- Field safety corrective action (FSCA) monitoring
23
Q
Medical device establishments
A
- Establishment license (for manufacturer, importer & wholesaler)
- QMS certification
24
Q
Regulatory control points to regulate medical devices
A
- Licensing of manufacture, import & supply
- Product registration (on Singapore Medical Devices Register SMDR, Class A exempted)
- Post-market records of recalls, distribution & advertisements
25
Types of registration in conformity assessment
- Registration of devices
| - Registration of persons
26
Mandatory requirements in Health Products Act
- Control supply chain via dealers & establishments
Dealer Licensing
- Legislation identify and define the joint responsibility of importers, authorised representatives and distributors
- All of them are governed by the legislation and must comply
- Responsibility period is for the entire lifetime of the device
27
Premarket control of medical device regulation (2 prong)
Dealer Licensing
- Manufacturer's License
- Importer's License
- Wholesaler's License
Product Registration
- Registered medical device for supply in
28
Dealer's Control
GDPMDS SS620:2016 is a requirement for all licensed local importers and wholesalers (auditable)
* ISO13485 for Manufacturers already covers the scope for GDPMDS
29
Good Distribution Practice for Medical Devices
- mandatory to importers & wholesaler
- ensures quality distribution system
- ensure a system to comply with post-market requirements, including AE reporting and FSCA
30
Distributor Activities
procurement, storage, distribution of medical devices in large quantities in accordance with legislation
31
Product Registration
- Phased in approach
- Higher risk C & D registered before A & B
- Authorised Representative (AR) responsible (does not need GDPMDS and are not top management)
32
How to register product
Singapore uses the CSDT – common submission dossier template for submission
33
Pharmaceutical Manufacturing
- Milling
- Drying
- Compresison
- Coating
34
Drug features
- Consists of therapeutics and excipients combined in a delivery system
- deliver drugs at certain rate determines drug success
- Active Pharmaceutical Ingredients (API): active ingredients in medicine
35
Good Manufacturing Processes (GMP) of drugs
* record keeping
* personnel qualifications
* sanitation
* cleanliness
* equipment verification
* process validation
* complaint handling
36
Sources of risks from drug products
- Avoidable & unavoidable known side effects
- Medication errors
- Product quality defects
37
Product/ Process development paradigm
- Manufacturing
- Process development & scale up
- Formulation
- Drug synthesis
38
Dosage Forms
- Tablet/ Capsules
- Injectables
- Inhalants
- Transdermal implants and products
39
Oral dosage forms
Tablets
- Lozenges
- Chewable tablets
- Effervescent tablets
- Multi-layer tablets
- Modified release
Capsule
- Hard gelatin
- Soft gelatin
Powder
40
Inhaled dosage forms
Aerosols
- Metered-dose inhalers
- Dry powder inhalers
41
Stages of pharmaceutical manufacturing
1. Starting materials (chemicals)
2. API
3. Finished product (includes exepients)
4. Primary packaging
5. Secondary packaging
42
What are excipients
- an inert substance added to the drug to give suitable consistency or definite form to the drug
- pharmaceutical necessity/ aid
43
Types of excipients
- Antioxidants
- Ointment base
*for compounding of the pharmaceutical dosage forms
44
Antioxidant
- inhibits oxidation
- added to prevent deterioration via oxidation
etc.
- the development of rancidity in oils and fats
- inactivation of some medicinal in the environment of their dosage form
Provides H+ electron to free radical to terminate chain reaction
45
Excipient list
Fillers:
increases weight and size of final dosage form
Binders:
promote particle aggregation
Disintegrants:
promote breakdown of aggregates
Flow aids:
reduce interaction between particles
Lubricants:
reduces interaction between particles and surfaces of processing equipment
Surfactants:
promotes wetting
Modified release agents:
influences the release of active
46
Solid Dosage Processing
Dosage forms
- Quality factors
Excipients
Particle properties
Processing routes
Unit operations
47
Quality factors for solid dosage forms
Functional quality factors
- Disintegrates to desired size quickly
- Dissolve and absorbed in the GI tract at a pre-determined rate
Physical quality factors
- withstand processing, packaging, transportation, dispensing or handling
- Surface must be free of defects
- Must be stable under anticipated environmental conditions
- consistent weight & composition for each pill
Sensorial quality factors
- Easy and pleasant to swallow
48
Product Functions
```
Product property
• Content uniformity
• Dissolution
• Flow-ability
• Dust formation
```
Particle Properties
• Particle size
• Particle shape
• Surface characteristics
49
Processing Routes
1. Wet granulation
2. Dry granulation
3. Direct compression
50
Unit Operations
Process function
– Process parameters: Type of unit operation, operational parameters
```
Type of unit operation
Size reduction (Milling)
– Blending
– Dry granulation (Roll compaction)
– Wet granulation
– Drying
– Tablet compression
– Coating
```
51
Who discovers drugs?
Identify biological target - biology
Prioritise/ validate target – pharmacology and chemistry
Identify and optimise lead molecules – chemistry/pharmacology
Preclinical studies – chemistry/pharmacology/ toxicology
Formulation - pharmaceutical sciences
Clinical evaluation – medicine
Manufacture - chemical engineering
52
Good Laboratory Practices (GLP)
quality system concerned with the organisational process & conditions under which nonclinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported
53
Objectives of GLP
- True reflection
- Ensure Honesty
- International acceptance
54
Scope of GLP (OECD)
```
applies to all non-clinical health and environmental safety studies required by regulations for the purpose of registering or
licensing
• Pharmaceuticals
• Pesticides
• Food and feed additives
• Cosmetic products
• Veterinary drug products and similar products
• Industrial chemicals
```
55
Organisation and Personnel
* Management’s Responsibilities
* Ensure sufficient number of qualified personnel, appropriate facilities, equipment, and materials
* Ensure the maintenance of a record of the qualifications, training, experience
* Proper training of personnel to assigned functions
* Job description for each professional and technical
* To establish and follow SOP
* Quality assurance program with designated personnel
56
Organisation and Personnel Study Director
responsible for the overall conduct of the non-clinical health and environmental safety
* Approval of protocols & the study plan including amendments
* Ensure QA personnel and study personnel are updated with study plans & SOP
* Ensure the follow up of SOPs periodically and take appropriate corrective action
* Archiving Raw data, supporting materials and final report
57
Organisation and Personnel Principal Investigator
• Ensures the study is conducted in accordance with GLP
58
Organisation and Personnel Study Personnel
* Recording of all raw data in compliance with the principles of GLP
* Deviations from the instructions to be reported the PI or SD
* Takes health precautions and personal safety
59
Quality Assurance Program
individual or a group designated by management to assure studies comply with GLP Principles
• Maintains copies of protocols & SOPs
• Inspects each laboratory and man at work
– Study-based inspections
– Facility-based inspections
– Process-based inspections
• Determines any deviation from approved protocol and report to SD, PI & management
• Prepare statements to be included in final report containing dates & types of inspection
60
Facilities
Test System Facilities
Archive Facilities
Waste Disposal
61
Test System Facility
* Sufficient amount of rooms and areas to assure isolation of test systems
* Adequately protected storage area separate from test systems
* Areas available for the diagnosis, treatment and control of diseases
62
Archive Facilities
• Secure storage and retrieval of study plans, raw data, final reports & specimens to prevent untimely deterioration
63
Waste Disposal
• Appropriate collection, storage & disposal facilities and decontamination procedures
64
Apparatus, Materials & Reagents
Apparatus:
- validated computerised systems should be of appropriate design & adequate capacity
- periodically inspected, cleaned, maintained and calibrated according to standard operating procedures
Materials & Reagents:
labelled to indicate identity, Conc, DOE & storage instructions
*Should not affect adversely with the test systems
65
Test Systems
Physical/Chemical
• appropriately designed apparatus
• Integrity of test systems to be ensured
Biological
• Proper storage, housing and handling conditions
• Isolation of newly received animals/plants for evaluation and acclimatisation
• Information regarding identity at the containers
• Records of source, date of arrival and arrival condition
• Interference & Contamination free test system
Medical Device Manufacturing Practice
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Decks in class (4)
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