Development of Vaccines for Australia:

TGA Regulations and Approval process

 

Arjun H. R.1, M. P. Venkatesh2

1Pharmaceutical Regulatory Affairs Group, Dept. of Pharmaceutics, JSS College of Pharmacy,

JSS Academy of Higher Education and Research, SS Nagar, Mysuru - 570015, Karnataka.

2Associate Professor, Dept. of Pharmaceutics, JSS College of Pharmacy,

JSS Academy of Higher Education and Research, SS Nagar, Mysuru - 570015, Karnataka.

*Corresponding Author E-mail: venkateshmpv@jssuni.edu.in

 

ABSTRACT:

Since Edward Jenner’s creation of vaccine 200 years ago, which been serving as a boon to mankind till today and being benefited by vaccination. Childhood vaccination is done for infectious disease like Polio, measles, rubella etc. Apart from these childhood vaccinations, vaccine for communicable diseases also been developed which is leading to improvement of quality and standard of life. In 20th century there are many modern methods and improvised methods for vaccine development and immunisation. With all improvised technique they need monitoring during their manufacture. Introduction of any new vaccine to the market requires registration, approval, licensing etc. Individual country regulations should be followed, guidelines to be adhered to and submit all required documents. Upon approval they can market their product with all legal rights. In Australia, Therapeutics Goods Administration (TGA) regulates the approval vaccines and medicines and some lifesaving drugs. TGA has introduced two new pathways for rapid approval for life saving drugs for emergency use. The main objective of rapid approval process is to make sooner available of drug sooner than the usual regulatory process.

 

KEYWORDS: Vaccines, Regulations, Approval, Australia, TGA.

 

 


INTRODUCTION: 

Objective: Main objective of the article is to study the regulatory approval process of Australia.

 

Different countries have different regulations process as per there countries. In Australia, TGA is the regulatory body which regulates approval and monitoring of adverse drug reaction, fees structure for application for registration of vaccine, steps involved in regulatory process, reporting in blue card.

 

Regulatory Authority in Australia:

Therapeutics Goods Administration (TGA) is medicines and therapeutic regulatory agency of Australian government which was established in 1989.

 

Any substance which is said to have a therapeutic effect comes under Therapeutics Goods Act 1989 or Therapeutics Regulation 1990.1

 

As a part of health department, TGA regulates quality, safety, supply, and advertising of medicine, blood product and other therapeutics. TGA assesses vaccine before they can be used in Australia. They rigorously assess vaccine for three most important things- Quality, Safety, and Efficacy. Vaccines are sustained in level as the other prescription medicines and other therapeutics goods.1

 

They assess the vaccine based on the best available evidence along with the risk and benefits of each vaccine. There evidence requirements are based on international guidance developed by European Medicine Agency. Clinical trials plays an important role assessing the risks and benefits. They are very closely monitored. They are well equipped with well-designed trials of sufficient length with enough people who represent the people for whom the vaccine is intended. It also advices the manufacturers to meet manufacturing quality standards. Laboratories will also assess the quality of every batch of vaccine before it is supplied in Australia. 1

 

Table 1: Different divisions and their support branches of TGA

Division name

Branch name

Medicines Regulation

Prescription Medicines Authorisation

Complementary and Over-the-counter Medicines

Scientific Evaluation

Pharmacovigilance and Special Access

Medical Devices and Product Quality

Medical Devices Authorisation

Medical Devices Surveillance

Laboratories

Manufacturing Quality

Regulatory Practice and Support

Regulatory Services and Drug Control[a]

Regulatory Compliance

Regulatory Engagement, Education and Planning

 

Monitoring of vaccines in Australia:

After the vaccines are approved for marketing in Australia, they are frequently assessed for their quality, safety, and efficacy. If adverse event experienced after the use of vaccine, the patient seeks the assistance from health professionals and report the adverse event to TGA.1

 

Adverse event reporting in Australia is mandatory to the company which supplies vaccine in Australia so that these companies develop and implement risk management for their vaccines. Australian laboratories help in monitoring vaccine safety; they also assess quality of vaccine batch wise. The quality of vaccine from selected batches are evaluated after they are supplied in Australia. If any problem is suspected with the vaccine, they launch an investigation. In some other cases, use of vaccine can be suspended during the investigation.

 

Received adverse event reports from consumer, health professional and the company which supplies vaccine and other health departments are published in Database of Adverse Event Notification (DEAN).1

 

TGA decision are informed by independent advice:2

Decision whether the vaccine should be approved for the use in Australia is informed by Advisory Committee on Vaccines (ACV). ACV is an independent committee appointed by Australian Government Minister of Health. It consists of expertise in science, medicine, and public health. ACV ensures that the assessments of vaccines are as robust as possible.2

 

Role of ACV: This committee is established under Regulation 39F of the TGR 1990 and members are appointed by Minister of Health. ACV was established in January 2017, with consolidation of previous functions of Advisory Committee on prescription Medicines (ACPM).

 

Stages of Vaccine approval in Australia:3

There are six stages in approval of vaccines

1. Pre-application

2. Application

3. Evaluation

4. Decision

5. Registration

6. Monitoring

 

STAGE1: Pre-application:

To file an application, sponsor must first submit a Provisional determination application. The application will be scrutinized by TGA against some marked criteria viz, nature of preliminary clinical data, evidence of plan to submit comprehensive clinical data and clinical also if needed.

 

Then TGA will grant a Provisional determination and then sponsor is eligible to apply the provisional registration of vaccine in Australian registration of Therapeutic Goods (ARTG).3

 

Purpose of provisional determination:

A sponsor will apply application for the determination and have approved application before they can lodge submission for provisional determination. Its formal process which allows to make a decision whether the medicine is eligible for the provisional approval pathway. Application is made by using a specified form requesting assessment against the eligibility criteria. This do not guarantee acceptance the submission for registration. The determination of application is made using a specified form with a relevant eligibility criterion and a decision of TGA (section 22C (2) of the Therapeutic Goods Act 1989.4

 

Benefits of determination:

This step ensures the access to the Provisional Pathway that meets the eligibility criteria; this also provides the consistent and transparent process for making assessment. The provisional pathway makes a way to the registration of the medicines which is based on preliminary clinical data. However, it also requires quality, GMP, and along with non-clinical data. These data are provided during the standard registration of vaccines also. Submission for the provisional determination is not given until and unless the provisional determination is it’s in place at the time when lodging the section 23 submission for registration. Also, the company or sponsor cannot lodge after the pre submission planning form. TGA will costs fees for all the activities that falls under the Therapeutic Goods Act 1989, the fee costs for service and the product evaluation. List of fees is scheduled in 9 and 9a Therapeutics Goods Act 1990. (Table 1)4

 

Figure 1: Provisional determination process diagram 4

 

Table 1: Details of Fees for Manufacturing biologicals as per TGA 6

Manufacturing biologicals

Fee

Schedule 9A Part 2

Australian manufacturing sites - application fee for a manufacturing licence

$1,130

Item 3

Initial manufacturing audit - inspection fee for Australian and overseas manufacturing sites

$22,300

Item 12

Subsequent manufacturing audit - inspection fee for Australian and overseas manufacturing sites

$16,900

Item 13

Inspection fee for each hour of preparation by each inspector for an inspection conducted outside Australia

$690 /hour/inspector

Item 14

Inspection fees to cover costs and reasonable expenses by each inspector, including costs for accommodation and allowance outside Australia

Costs and reasonable expenses

Item 15

 

These fees are in Schedule 9A, Therapeutic Goods Regulations 1990

 

TGA assessment of determination application:

The given timeframe for the application assessment is 20 working days. The process starts from the day of payment for the determination fees and the time starts from the determination of application receipt. Finally, assessment begins from working after the fee payment.After submitting the e-form of the determination application, TGA will assess the given information whether it is sufficient or not to begin the assessment of the application.7

 

Assessment of the application involves:

·       Check for the issued invoice

·       Check for the details in application with clear and robust scientific justifications.

·       Justifications are up to date

·       Reference and supporting data

·       For any queries during assessment the applicant can contact at AET.Application.Entry.Team@health.gov.au7

 

How they will assess:

They review the application eligibility criteria in regulation 10K and 10L.  The focus of the assessment is to determine the application meets eligibility criteria with all supporting documents which is establishing the eligibility criteria. They may approach to an expert’s advice in some aspects if they required. Clinical Evaluation Unit will be supervised by Chief Medical Advisor, who is concerned as decision maker for the application determination process. 7

 

Notifying the sponsor about decision:

After assessment of the application and if it meets the determination application criteria then final decision will be made. After final decision, the outcome is informed to applicant through a mail id mentioned in application under subsection 22D (4) of the Act. 7

 

Information included in the approval letter include the name of the applicant (sponsor), the name of the medicine, each active ingredient of the medicine and the provisional indication 7

 

If case of rejection of application, the reasons for the decision and the details of rights to appeal the decision will be included in the letter. 7

 

Figure 2: Timeframe of each Phases [8]

 

STAGE 2: Application:

Once the provisional determination has granted a sponsor need to apply for a provisional registration in the ARTG (Australian Register of therapeutic goods). To register a vaccine in Australia, sponsor or applicant need to submit a dossier which enclosed with specific information about non-clinical, clinical, toxicological studies, manufacturing, risk management and other relevant information. TGA accepts only limited number of submissions of data during the evaluation phase. Then TGA will conduct a preliminary assessment whether to accept the submitted application for evaluation or not and they will notify sponsor.9

 

Quality and Non-clinical Data:

A sponsor should include data regarding quality and non-clinical safety modules (Safety module 3 and 4) in their dossier which fulfils the mandatory requirements of data and scientific guidelines as per the European Union and International Conference on Harmonisation (ICH).10

 

STAGE 3: Evaluation:

After accepting the application, TGA will organise a formal evaluation process which is carried out in multiple phases by the organised technical experts. This stage involves obtaining the requisite information and clarification from the applicant or sponsor as well as being informed by ACV (advisory committee on vaccines) and an external independent expert.11

 

TGA mainly assess for the quality, safety, and effectiveness of the main ingredient of the vaccine before the registration of vaccine in Australia. Also, they evaluate the conducted clinical trials. The conduct and plan of clinical trials are evaluated with sufficient time or not also the number of participants. The vaccine manufacturers should meet the manufacturing standards. They also assess the quality of vaccine from every batch before they are supplied in Australia. They also closely work with international collaboration and share the information.12

 

STAGE 4: Decision:

Once the evaluation done by the experts, TGA delegate will make an important decision whether to provisionally register the vaccine in ARTG or not.13

Decision is granted on the following factors:13

·       Safety, quality, and effectiveness of the vaccine.

·       Vaccine should meet all standards laid down in by guidelines.

·       Sponsor has submitted clinical data, stability data, and other relevant information.

 

STAGE 5: Registration:

Once it has got approved, it is considered as provisionally registered in ARTG and once sponsor get the approval letter from TGA they can lawfully market their vaccine in Australia market. Approved vaccine can be found to ARTG on the official website (TGA) along with this, product information is also available Med Search app and other registered vaccines.13

 

The provisional registration is initially only up to two years and sponsor can also apply for two more extensions, maximum of up to six years.13

·       AUST L 'listed' medicines, which have not been assessed for efficacy

·       AUST L (A) 'assessed listed' medicines, which have had their health claims assessed for efficacy.14

 

STAGE 6: Monitoring:

TGA plays an important role in safety monitoring of vaccines which are available in Australia; they have robust procedures to investigate any vaccine safety issues in Australia. TGA vaccine safety monitoring system will rapidly detect any safety issues regarding the vaccine and thorough investigation will be done for the safety issue raised in Australia.15

 

Adverse Event Reporting in Australia:

Adverse events are one which occurs unintendedly and sometimes it may be harmful and may even cause death of the person. They are caused due to the vaccine administration.16

 

Example: Any reaction which is unfavourable and unintended symptom, sign or the disease caused due to administration of Therapeutic goods. Unfavourable conditions can be found out by laboratory tests.16

 

Adverse Event Reporting in Australia:

Adverse events are one which occurs unintendedly and sometimes it may be harmful and may even cause death of the person. They are caused due to the vaccine administration.16

 

Example:

Any reaction which is unfavourable and unintended symptom, sign or the disease caused due to administration of Therapeutic goods. Unfavourable conditions can be found out by laboratory tests.16

 

Mainly adverse events are not caused only due to the administration of therapeutic good, it may be also due to other interaction or any other unrelated conditions. The cause or any unfavourable condition is not only due to the administration of therapeutic good always. In such case, an individual can report that adverse event or unintended sign or symptom in Australia to TGA.16

 

In Australia side effects reporting is managed and maintained by Database of Adverse Event Notification (DAEN). Reports come from various sources which includes general public, medical practitioners, industries, nurses, and ay health professionals.16

 

Blue Card Adverse Reaction Reporting Form: This form is used to report the adverse reaction or side effects of vaccines, prescription, and OTC medications.17

 

CONCLUSION:

In this article, we have discussed the regulatory process which is carried out by Therapeutics Goods Administration (TGA) for vaccine, regarding structure of TGA, fees structure, description about steps involved in approval process. Once it is approved for marketing, it is monitored for its adverse effect and reporting of adverse effects plays an important role. Reporting of adverse event is done through Blue Card form in Australia.  

 

REFERENCES:

1.     HTTPS://WWW.RACGP.ORG.AU/AFP/2015/NOVEMBER/VACCINATION-AND-THE-LAW/[INTERNET] [15/03/21]

2.     HTTPS://WWW.TGA.GOV.AU/NODE/734378  [INTERNET] [15/03/21]

3.     https://www.tga.gov.au/covid-19-vaccine-approval-process  [INTERNET] [30/04/21]

4.     https://www.tga.gov.au/publication/provisional-determination [INTERNET] [01/05/21]

5.     https://www.tga.gov.au/node/905802 (SUMMARY OF FEES TABLE)[INTERNET] [ 01/05/21]

6.     HTTPS://WWW.TGA.GOV.AU/SITES/DEFAULT/FILES/CREDIT-CARD-PAYMENT-AUTHORISATION-200629.PDF [INTERNET] [05/05/21]

7.     https://www.tga.gov.au/publication/provisional-determination [INTERNET] [10/05/21]

8.     HTTPS://www.tga.gov.au/node/840831 [INTERNET] [11/05/21]

9.     https://www.tga.gov.au/covid-19-vaccine-approval-process  [INTERNET] [13/05/21]

10.  HTTPS://www.tga.gov.au/node/840851 [INTERNET] [17/05/21]

11.  https://www.tga.gov.au/covid-19-vaccine-approval-process  [INTERNET] [20/05/21]

12.  https://www.tga.gov.au/covid-19-vaccine-information-consumers-and-health-professionals  [INTERNET] [25/05/21]

13.  https://www.tga.gov.au/covid-19-vaccine-approval-process  [INTERNET] [30/05/21]

14.  https://www.tga.gov.au/node/874691 [INTERNET] [04/06/21]

15.  https://www.tga.gov.au/node/913615[INTERNET] [10/06/21]

16.  https://www.tga.gov.au/node/3297 [12/3/06/21]

17.  https://www.tga.gov.au/sites/default/files/blue-card-adverse-reaction-reporting-form. [15/06/21]

 

 

 

 

 

 

Received on 20.09.2021             Modified on 22.04.2022

Accepted on 10.10.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(3):1491-1495.

DOI: 10.52711/0974-360X.2023.00245