registration of class b medical devices guidance for ... · conformity to us fda quality system...

of 13

Registration of Class B Medical Devices – 1

Guidance for Industry Consultation 2

3

1 BACKGROUND 4

5

Medical devices are classified based on a rule based risk classification system into 6 four risk classes – class A to D with class A being the lowest risk class and this is in 7 line with the recommendations from the Global Harmonization Task Force (GHTF). 8 The actual risk classification of each medical device depends on the claims made by 9 the product owner and on its intended purpose. Class B medical devices are typically 10

of low-moderate risk and includes devices such as hypodermic needles, suction 11 apparatus, pregnancy test kits and ultrasound imaging equipment. 12

13

2 EVALUATION ROUTES 14

15

Currently, there are two evaluation routes for Class B medical devices: 16

(i) Full Evaluation Route 17

(ii) Abridged Evaluation Route 18

19

With the enhancements to the medical device regulatory framework announced on 20

20 April 2012, there will be two more evaluation routes for Class B medical devices:- 21

22

(i) Expedited Class B Registration (EBR) Evaluation Route 23

(ii) Immediate Class B Registration (IBR) Evaluation Route 24

25

The eligibility for the different evaluation routes depends on the numbers of prior 26

approvals obtained from HSA’s reference agencies at the point of submission. The 27

types of approvals that qualify for abridged, EBR and IBR evaluation routes are: 28

Australia Therapeutic Goods Administration (TGA) 29

Health Canada (HC) 30

Japan Ministry of Health, Labour and Welfare (MHLW) 31

o Pre-Market Certification from a Japanese Registered Certification 32

Body; OR 33

o Pre-Market Approval from MHLW 34

US Food and Drug Administration (US FDA) 35

o 510K clearance 36

o PMA 37

European Union Notified Bodies (NB) via EC certificates issued according 38

to 39

of 13

o Directive 93/42/EEC Annex II section 3 or Annex V for Class IIA 40

devices 41

o Directive 98/79/EC Annex IV including sections 4 and 6 for List A 42

IVDs 43

o Directive 98/79/EC Annex IV or Annex V with Annex VII for List B 44

and self-testing IVDs 45

46

2.1 Full Evaluation Route 47

A medical device that has not obtained any prior approval from any HSA’s 48

reference agencies at the point of application will be subject to full evaluation route. 49

50

2.1.1 Submission Requirements 51

Letter of Authorisation 52

Annex 2: List of configurations of medical devices to be registered 53

Common Submission Dossier Template (CSDT) 54

a) Executive Summary 55

b) Essentials Principles Checklist and Declaration of Conformity 56

c) Device Description 57

d) Detailed Information of Design Verification and Validation Documents 58

− Full reports of Preclinical Studies including the detailed sterilization 59

validation if applicable 60

− Clinical Evidence, including publications and full reports of the 61

studies referenced in the clinical evaluation report 62

e) Proposed Device Labeling 63

f) Risk Analysis 64

g) Manufacturer Information 65

− Name and address of the manufacturing site(s) 66

− Proof of Quality Management System – e.g. ISO13485 Certificate, 67

Conformity to US FDA Quality System Regulations or Japan MHLW 68

Ordinance 169 69

− Manufacturing Process – Flow Chart 70

71

For medical device with label claims beyond the inherent performance of the device, 72

additional clinical data may be requested to substantiate the proposed label use. 73

of 13

74

2.1.2 Processing of application 75

76

77

78

Upon submission via MEDICS, an application fee will be charged immediately. The 79

application dossier will be verified for completeness before the application is 80

accepted for evaluation. Any omitted documents will need to be addressed via input 81

requests. 82

Upon acceptance of the dossier for evaluation, the evaluation fees will be triggered. 83

The payment mode (GIRO or progressive payment or others) will depend on the 84

applicant’s selection at the point of submission in MEDICS. 85

Evaluation of the dossier by HSA is based on the data set submitted by the applicant. 86

An input request will be issued to the applicant if clarification or additional information 87

is required. A regulatory decision is made based on the outcome of HSA’s evaluation 88

of the submitted dossier. Only application which satisfy the registration requirement 89

will be listed on the Singapore Medical Device Register (SMDR). 90

The stop-clock starts whenever HSA issues an input request and ends when HSA 91

receives a complete and satisfactory response from the applicant. 92

93

2.2 Abridged Evaluation Route 94

A medical device that has obtained at least one reference agency approval for a 95

labeled use similar to that intended for marketing in Singapore at the time of 96

submission will qualify for the abridged evaluation route. 97



Annex 2: List of configurations of medical devices to be registered 100

Proof of approval by reference agency (e.g. approval letters, certificates) 101



Submission of

application

via MEDICS

Evaluation of

application

Regulatory decision and

listing on SMDR for

successful registration

Verification

of application

of 13

b) Essential Principles Checklist and Declaration of Conformity 104


d) Summary of Design Verification and Validation Documents 106

− Summary of Preclinical Studies including the sterilization validation if 107

applicable 108

− Clinical Evidence 109


f) Risk Analysis (if applicable) 111


− Name and address of the manufacturing site(s) 113

− Proof of Quality Management System – Eg: ISO13485 Certificate, 114


Ordinance 169 116

117



120


122

123

124


application dossier will be verified for completeness before the application is 126

accepted for evaluation. Any omitted documents will need to be addressed via input 127

requests. 128

Upon acceptance of the dossier for evaluation, the evaluation fees will be triggered. 129

The payment mode (GIRO orprogressive payment or others) will depend on the 130

applicant’s selection at the point of submission in MEDICS. 131





will be listed on the SMDR. 136

Submission of

application

via MEDICS

Evaluation of

application


listing on SMDR for


Verification

of application

of 13



139

140

2.3 Expedited Class B Registration (EBR) Evaluation Route 141

(NEW for industry’s feedback) 142

143 2.3.1 Eligibility Criteria 144 145

The following medical devices are eligible for submission via the EBR evaluation 146

route: 147

148

(A) EBR-1: a medical device that has 149

obtained approval from at least one of HSA’s independent reference agencies for 150

a labeled use similar to that intended for marketing in Singapore; and 151

[HSA’s independent reference regulatory agencies are HC, MHLW, US FDA and 152

TGA/EU NB and the corresponding approvals listed under Section 2 Evaluation 153

Route] 154

been marketed for at least 3 years in the above independent reference agency’ 155

jurisdiction [or in Singapore]1; and 156

no safety issues globally, defined as 157

a) no deaths; 158

b) no serious deterioration in the state of health2 globally, 159

160

arising from the use of the medical device(s) as intended by the Product Owner, in 161

the last three years; and 162

163

c) no open field safety corrective actions (including recalls) at the point of 164

submission 165

OR 166

1 Or the medical device has been used in Singapore for at least 3 years prior to the implementation of requirement for

product registration for Class B medical devices on 1st January 2012

2 Serious deterioration in the state of health, in relation to a person means: (a) a life-threatening illness or injury suffered

by that person; (b) a permanent impairment of a bodily function of that person; (c) any permanent damage to any part of that person’s body; or (d) a condition requiring medical or surgical intervention to prevent any such permanent impairment or damage.

of 13

(B) EBR-2: a medical device that has obtained approval from at least two of HSA’s 167

independent reference agencies for a labeled use similar to that intended for 168

marketing in Singapore. 169



Annex 2 List of configurations of medical devices to be registered 172

Proof of approval from independent reference agencies – [Note: one independent 173

reference agency for EBR-1 and two independent reference agencies for EBR-2] 174

Proof of marketing history in the same independent reference agency’ 175

jurisdictions e.g. Invoice with date, proof of sale – [Note: for EBR-1 only] 176

Declaration of no safety issue globally (Refer to Annex C for the template for this 177

declaration) – [Note: for EBR-1 only] 178



b) Essentials Principles Checklist and Declaration of Conformity 181


d) Summary of Design Verification and Validation Documents 183

− Summary of Preclinical Studies including summary of sterilization 184

validation if applicable 185

− Clinical Evidence 186


f) Risk Analysis (if applicable) 188


- Name and address of the manufacturing site(s) 190

- Proof of Quality Management System – e.g. ISO13485 Certificate, 191


Ordinance 169 193

194



197


of 13

199

200

201


application will be verified for eligibility for EBR and once confirmed, the application 203

will be accepted for evaluation. The evaluation fees will be charged at this point. In 204

view of the shortened processing timeline, progressive payment will not be an option 205

available for applications submitted via this route. In the event that the application 206

does not qualify for EBR, the application will be re-routed to the abridged evaluation 207

route and the respective evaluation fee shall apply. 208





will be listed on the SMDR. 213



216

2.4 Immediate Class B Registration (IBR) Evaluation Route 217

(NEW for industry’s feedback) 218

219

2.4.1 Eligibility Criteria 220

221 222

A medical device that fulfils the following criteria will be eligible for IBR: 223 224

approval by at least two of HSA’s independent reference agencies for intended 225

use similar to that submitting for registration in Singapore; and 226

marketed for at least 3 years in both independent reference agencies’ 227

jurisdictions; and 228

no safety issues globally, defined as 229

a) no deaths; 230

b) no serious deterioration in the state of health2 231

232

globally, arising from the use of the medical device(s) as intended by the Product 233

Owner, in the last three years; and 234

235

Submission of

application

via MEDICS

Evaluation of

application


listing on SMDR for


Verification

of application

of 13

c) no open field safety corrective actions (including recalls) at the point of 236

submission 237

238

In addition, the medical device should not have any rejection/withdrawal in any 239

reference agency or prior rejection/withdrawal in Singapore. 240

HSA’s independent reference regulatory agencies are HC, MHLW, US FDA and 241

TGA/EU NB and the corresponding approvals listed under Section 2 Evaluation 242

Route. 243

244



Annex 2 List of configurations of medical devices to be registered 247

Proof of approval from independent reference agencies 248

Proof of marketing history in the same two independent reference agencies’ 249

jurisdictions e.g. Invoice with date, proof of sale 250

Declaration of no safety issue globally (See Annex C for the template for this 251

declaration) 252

Common Submission Dossier Template (CSDT): 253

a) Executive summary 254

b) Device description 255

c) For sterile device only: declaration of conformity to ISO sterilization 256

standards for sterile medical devices. If not in conformity to ISO 257

sterilization standards, a summary of sterilization validation is required. 258

d) Proposed device labeling 259

e) Manufacturer Information 260

- Name and address of the manufacturing site(s) 261

- Proof of Quality Management System – Eg: ISO13485 Certificate, 262


Ordinance 169 264


additional clinical data may be requested post-registration to substantiate the 266

proposed label use. 267

of 13


269

270

Upon successful submission via the MEDICS, the medical device will be listed on the 271

SMDR immediately. The total fees will also be charged immediately upon successful 272

submission for this route. As the device is listed immediately upon successful 273

submission, applicants are reminded to ensure that all the required information is 274

entered correctly and accurately. 275

HSA will verify the documents submitted in MEDICS after successful submission. 276

Based on the intended use of the device by the Product Owner, additional licensing 277

conditions may be imposed post-registration. 278

The IBR evaluation route facilitates immediate market access for the medical devices. 279

Any IBR application which fails to fulfill ALL criteria specified under section 2.4.1 for 280

the IBR evaluation route, not supported by the correct documents or a wrong risk 281

class medical device submitted via the IBR evaluation route will result in cancellation 282

of registration and total registration fee will NOT be refunded. This device will have 283

to be re-submitted via other evaluation routes or submitted as other risk class. In 284

these cases, the corresponding new application and evaluation fees shall apply. 285

286

3 GENERAL NOTES 287

All aspects of the medical device’s quality including packaging, labelling (including 288

instruction of use), and intended purpose/indications for use, intended for supply in 289

Singapore shall be the same as that approved by the reference agencies that have 290

approved the medical device. Registrants are required to attach appropriate 291

explanation if there are differences from those stated in the certificates or the 292

reference agency approved labelling. 293

For further information on the specific content and requirements for the letter of 294

authorization and CSDT, please refer to GN-15, GN-17 and GN-18 guidance 295

documents, respectively. 296

A summary of the evaluation routes and its corresponding documentation 297

requirements is attached in Annex A and B respectively. 298

299

Successful submission

of application via

MEDICS

Completion of

registration and

listing on SMDR

Verification of

documents

of 13

Annex A 300

Summary of Evaluation Routes 301

Evaluation Route

Full Abridged Expedited Class B registration - EBR

(NEW for industry’s feedback)

Immediate Class B registration – IBR


Criteria

(at the time of submission)

Not approved by any of HSA medical device’s reference agencies

At least 1

reference

agency’s

approval

EBR – 1

At least 1 reference

independent

agency’s approval

Marketed for ≥ 3

years in the above

independent

reference agency’s

jurisdiction*

No safety issues

globally

OR

EBR-2

At least 2 independent reference agencies approvals

At least 2

independent

reference

agencies’

approvals

Marketed for ≥ 3

years in the

above 2

independent

reference

agencies’

jurisdiction

No safety issues globally

No prior rejection/withdrawal by independent reference agencies and Singapore

Targeted Turn-Around-Time

160 working days#

100 working days#

60 working days# Immediate listing upon

successful submission in MEDICS

Total Fee S$4,000 S$2,300 S$1,400 S$1,400

*Or the medical device has been used in Singapore prior to the implementation of requirement for 302 product registration for Class B medical devices on 1st January 2012 303 #Excluding company’s response time to input request 304 305 306

307 308 309 310

of 13

Annex B 311

Summary of Submission Requirements 312

Documentary Requirements Full Abridged

EBR -1 and 2


IBR (NEW for industry’s feedback)

1 Letter of authorization

2 Annex 2 List of Configurations

3 Proof of reference agency’s approval(s)

4 Proof of marketing history in the reference agencies’ jurisdictions e.g. Invoice with date,

Only

required for

EBR-1

5 Declaration of no safety issues globally

6 Executive Summary

7 Essential Principles Checklist and Declaration of conformity

8 Device description

9

Design verification and validation documents including :

o Preclinical studies o Clinical evidence

Detailed reports1

Summary2

Summary2

Sterilisation validation for Sterile device

only3

10 Proposed device Labelling4

11 Risk Analysis

If applicable If applicable

12 Manufacturing site’s name and address

13

− Proof of Quality Management

System – Eg: ISO13485

Certificate, Conformity to US

FDA Quality System

Regulations or Japan MHLW

Ordinance 169

14 Manufacturing Process – Flow

Chart

1 Full study reports containing complete descriptions of the objectives, protocols, methods of data 313 analysis, results and conclusions are to be provided. 314 2 A summary of the studies undertaken is to be provided and should include a brief description of 315 the study objectives, test methods, results and conclusions. 316 3 A declaration of conformity to ISO Sterilization standards is acceptable. If not, a summary report of 317 sterilisation validation is required. 318

of 13

4 Medical device with label claims beyond the inherent performance of the device, additional clinical 319

data may be requested to substantiate the proposed label use. For medical device submitted via 320

IBR route, the additional data may be request post registration. 321 322

of 13

Annex C 323

Safety Declaration Template 324 325

[To be printed on Company Letterhead of Registrant] 326

Medical Device Branch 327 Pre-Marketing Division 328 Health Products Regulation Group 329 Health Sciences Authority 330 331 [Date] 332

333

Dear Sir/Madam, 334

335 Subject: Declaration of no safety concerns 336 337 I, [name of Registrant], the applicant for registration of the medical device(s) stated below, hereby 338 declare that there are: 339 340

No deaths 341 342

No serious deterioration in the state of health1 343 344 globally, arising from the use of the medical device(s) when used as intended by the Product Owner, 345 in the last three years from dd/mm/yyyy]; and 346 347

No open field safety corrective actions (including recalls) 348 349 This declaration shall apply to the following medical device(s): 350 351 [List containing product names of medical devices] 352 353 354 I, the applicant, am aware that a false declaration is an offence under the Health Products Act (Cap. 355 122D) and may result in the cancellation of registration of the above medical devices under Section 356 37(1) of the Act. 357 358 Yours Sincerely, 359 360 [Signature] 361 362 [Full Name and Title of Senior Company Official] 363 364 [Company stamp] 365 366 ------ 367 1 Serious deterioration in the state of health, in relation to a person means: (a) a life-threatening illness or injury suffered 368

by that person; (b) a permanent impairment of a bodily function of that person; (c) any permanent damage to any part of 369 that person’s body; or (d) a condition requiring medical or surgical intervention to prevent any such permanent impairment 370 or damage 371