호주에서의 임상시험 - TGA 에 통보 및 보고하기

임상시험을 하다가 대만이나 태국, 홍콩 등과 엮이게 되면 - 사실은 한국 식약처에서 승인을 받고 진행해야 하는 것을 포함한 여러 과정들이 비슷한게 많아서 이해하고 받아들이기가 쉬운데, 호주랑 임상시험이 엮이면 그렇지는 않은거 같습니다. 저는 처음 호주랑 임상시험으로 엮이게 됐을 때 한국의 식약처에 준하는 호주의 TGA가 임상시험 계획서를 검토하고 승인하는게 아니라 - TGA에 통보하고 돈만 내면 된다고 해서 아주 당황했었습니다. 당시 제 눈엔 자국민 보호(?) 같은건  없고 그냥 수수료만 받아 챙기고 하라는거 같았거든요. 

호주의 TGA가 통보만 받는 이유는 임상시험을 진행하기 위해서는 스폰서가 NHMRC (National Health and Medical Research Council)의 가이드 라인을 따르는 윤리위원회의 (Ethics Committee)의 사전승인을 받아야 한다고 못박아두었기 때문입니다. 연구 계획이나 동의서, 기타 등등은 모두 윤리 위원회가 알아서 검토하라는 겁니다. 어떻게 보면 효율적이지만, 어떻게 보면 여전히 무책임한 것 같습니다. 미국 FDA도, 유럽의 EMA (European Medicinal Agency), 하다못해 바로 옆 뉴질랜드도 MedSafe에서는 윤리 위원회의 승인을 받는 것에 더해 국가 레벨의 규제기관에서도 승인을 받고 임상시험을 진행하도록 하고 있거든요. 

호주 같이 통보만 해도 되는 나라는 - 호주 말고는 아직 못봤습니다. 아무튼 이러한 효율성을  이유로 중국계 바이오벤처 회사들이 호주에서 1상 및 2상 임상시험을 진행하는 것을 심심치 않게 볼 수 있습니다. 물론 거의 같은 시간대라는 것과, 가깝다는 것, 그리고 다양한 인종의 데이타를 모을 수 있다는 것도 한몫하겠죠. 

아무튼 오늘은 저도 머릿속으로 정리도 할겸 호주에서 임상시험을 진행할때 필요한 TGA notification process를 정리해 보았습니다. 

글의 순서

1. Regulatory Overview Australia

2. Initial Submission

3. Amendment Submission

4. Reporting Requirements

5. Useful Links

 

1. Regulatory Overview Australia

TGA (Therapeutic Goods Administration)

• Australian Medicines & Medical Devices Safety Authority

• Part of Department of Health

• Administers the clinical trial application & approval process

• Responsible for regulating the supply, import, export, manufacturing and advertising of therapeutic goods

• Does not provide approval for a clinical trial but instead an Acknowledgement of Receipt (AoR) of the Clinical Trial Notification (CTN)

• Most clinical trials generally do not complete Clinical Trial Exemptions (CTX)

• The TGA safeguards and enhances the health of the Australian community through effective and timely regulation of therapeutic goods.

• The TGA takes a risk-based approach to regulation

 

2. Initial Submission

• Electronic via TGA Business Services Website: https://business.tga.gov.au/

• Can be done in parallel with Ethics

• No submission deadlines or meeting dates

• We generally receive AoR within 10 calendar days

• Fee for initial / amendment applications

• Completion Guidance - key points:

• Refer to the Clinical Trial Notification (CTN) form: user guide found on the website
• Can also refer to published videos explaining the online CTN form: Video 1: Creating and submitting a Clinical Trial Notification (CTN) and Video 2: Invoicing and the role of the Clinical Trials Repository
• Title of Study should be exact title per Protocol, do not use a lay title. 
• Total number of participants to be enrolled in the Trial = Estimated total number of participants to be enrolled in the trial in Australia only.
• Medicine Details –

• Trade Name/Product Name/Code Name
• Each trial medicine must be entered in separately, this extends to different strengths of the same product.
• Manufacturer details only to be included if manufactured in Australia.
• Placebos must be declared on the CTN (Does not matter what the sourcing arrangements are).
• Please note that the TGA’s definition confirms that medicines of biological origin are not considered biological - monoclonal antibody is not always biological drug under TGA classification.  In contrast, AQIS (Australia Quarantine Inspection Service) consider anything of biological origin to be biological and therefore, monoclonal antibody importation requires import permit.
• Indication =  The specific therapeutic use of the goods in this clinical trial (i.e. the 'intended' indication per the protocol, not the ARTG indication)
• Device Details –
• Electronic patient reported outcomes, study questionnaires and patient diaries do not need to be declared on the CTN (unless the e-PRO contains a form that has a diagnostic component)
• Centrally provided medical devices must be declared as a Medical Device, as not manufactured in Australia and used for diagnostic purposes.
• Centrally supplied Laboratory Kits (which covers central pregnancy kits) must be declared as a Medical Device, as not manufactured in Australia and used for diagnostic purposes. Declared as a Medical Device
• Product Name = Laboratory Testing Kit (do not include vendor name)
• Is this a = Procedure Pack
• Manufacturer  = Legal entity name of Central Laboratory [Although not marked with an *, this is a mandatory field as advised by TGA (portal not updated).]
• TGA’s definition of Manufacturer: https://www.tga.gov.au/acronyms-glossary#summary-m
• Due to broad definition (which captures both production and supply), we are confident that by using supplier name for “Manufacturer” we are disclosing sufficient information to the TGA. Suppliers have a responsibility to manage any issues with their stock should an issue or recall arise.
• E.g. For Centrally supplied Laboratory Kits, the supplier may be LabCorp, Quintiles, Covance, ICON, PPD, however the manufacturer of the tubes would a be a number of companies like BD, Sastedt, etc. Thus appropriate to use overarching supplier name instead of listing all individual manufacturer companies.




• Description = Laboratory Testing Kit
• Intended Purpose =  Other - Laboratory testing kit used for trial participants for the purpose of diagnosis, prevention, monitoring, treatment or alleviation of disease.
• GMDN name and description = Not applicable
• Countries Selected = All countries confirmed in final allocation.
• Trial Site Details:
• Location(s) where trial-related activities are actually conducted
• Sponsor stance on declaration of sites and pharmacies on the CTN:
• Please include:
• Sites that the sponsor have directly contracted with for the study. This includes directly contracted pharmacies  (whereby  chain of custody for drug management has been broken by the sponsor)
• Sites where participants are being administered treatment  at the site or where significant study procedures are taking place (this may also include 'satellite sites')
• HREC/RGO approval is not required in order to submit a CTN - “The TGA has no issues with the submission of the CTN form whilst the sponsor is obtaining the necessary endorsements. However, it is the responsibility of the sponsor to ensure that all relevant approvals are in place before supplying the therapeutic goods in the clinical trial.”

 

3. Amendment Submission

Amendments only required when:

• Change to Protocol Title
• Addition of new site(s) to a previously notified trial
• Changes to previously notified therapeutic goods that creates separate and distinct goods
• Addition of a new therapeutic good to a previously notified trial

Key points:

• A fee will be incurred
• Please submit the relevant payment to TGA Accounts Receivable as per the information of the TGA Payment Options webpage

 

4. Reporting

There is no requirement to provide an annual report to the TGA.

There is no requirement to submit Protocol amendments or Investigator Brochure updates to the TGA.

There is no requirement to submit adverse events to the TGA. This is handled by the Regulatory Affairs department and forms part of a much larger reporting system for the entire business.

 

5. Useful Links

TGA https://business.tga.gov.au/

Consolidated the online Clinical Trial Notification (CTN) form guidance documents into one guidance document the Clinical Trial Notification (CTN) form: user guide

 Published videos explaining the online CTN form: Video 1: Creating and submitting a Clinical Trial Notification (CTN) and Video 2: Invoicing and the role of the Clinical Trials Repository

모쪼록 임상업계에 계신 분들, 호주와 임상시험으로 엮이는 분들께 도움이 되길 바래요!