Update on regulatory reforms from the Scientific Evaluation Branch - - PowerPoint PPT Presentation

Update on regulatory reforms

from the Scientific Evaluation Branch

Jenny Burnett Scientific Operations Management Section Scientific Evaluation Branch Medicines Regulation Division, TGA ARCS August 2019, Sydney

Outline

• The latest on variations
• Generic Medicines Reform Program
• Human cells and tissue regulation (excluded goods)
• Faecal Microbiota Transplantation
• 2D DataMatrix codes for medicines

1

The latest on variations

2

Variations to registered medicines

Our philosophy is – Continuous improvement Thoughts from last year…

• Possible new notifications
• Enhancements to the e-form
• More moves from paper to electronic applications

So what happened next??

3

Possible new notifications?

• Requires amendment to the Regulations
• Legislation changes require consultation
• More complex situations …

– Variations affecting Product Information

• Complex from regulatory perspective
• other projects affecting PIs already underway

– Changes to low risk ingredients

• Requires an Act amendment

Complexity = Time delay

4

Now the good news!

Enhancements to the e-form for prescription medicines

• Clarity on retaining existing AUST R number
• ‘associated changes’
• Automated removal of manufacturers with

invalid GMP Updated guidance

• Multiple related changes
• Multiple unrelated changes
• Considerations prior to submission

5

“We have multiple changes …”

New separate and distinct goods? New AUST R? Associated changes Z codes Any link between the changes? An ‘event’ Consequential or related changes Same aspect of the goods

6

The importance of ‘conditions’

• Conditions listed under each variation type
• Notification/ SAR conditions not met requires category 3 application

Example LOTG: Label - changes to comply with current TGOs for labels that have previously been evaluated and approved by the TGA Conditions

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels

and not contravene labelling best practice.

If conditions not met LCDE: Label changes - any changes requiring data for evaluation

7

More good news!!

More applications can be made using the e-form

• Extension of Indications for

generic medicines

• Formulation changes -

flavours, fragrances, inks

8

• The latest on variations
• Generic Medicines Reform Program

9

A program of reforms

Public consultation

• Revised requirements for use of an
• verseas reference product
• New templates for bioequivalence data
• New process for ‘early advice’
• Incentives for medicines of special interest

Use of an overseas reference product

• The overseas reference product must be identical to the Australian reference product
• Evidence required includes:

Product labels Dissolution data Physical characteristics Quantitative analysis

• f components

What evidence should be provided to demonstrate identicality of reference products?

11

Consultation Outcomes

Use of overseas reference product

• Feedback

– Reduce Australian-specific requirements – Harmonise with other regulators where possible – Must not adversely affect quality and safety of generic medicines supplied in Australia

• Outcome

– Develop a risk-based approach – Reduced requirements for simple, low risk products – All current requirements remain for higher risk medicines

12

New templates for bioequivalence (BE) data

International templates

• Internationally-used templates will:

– Create greater consistency – Provide a checklist for applicants

• We have identified the following international templates:

– Bioequivalence study information – Biowaiver justification templates

13

Consultation Outcomes

BE templates

• Feedback

– Some support for adopting internationally-used templates – Must not result in additional re-work of dossiers for submission to the TGA – Align with EU and ICH requirements, remove Australian-specific requirements

• Outcome

– Drafted 3 new templates based on those developed by comparable overseas regulators – Created new guidance material – Considered implications for dossier content

14

New process for ‘early advice’

Early advice on biowaiver justifications

Aspects to be considered:

• Explicit and limited number of technical

issues specific to biowaiver justifications

• No additional regulatory burden
• Possible future broader use

15

Consultation Outcomes

Early advice process

• Feedback

– All submissions were supportive – Advice needs to be ‘binding’ – Appropriate that a fee is charged – Should be available for a range of topics

• Outcome

– Amendment to the Therapeutic Goods Act 1989 – Restricted to biowaiver justifications (in the first instance) – Need industry involvement to ensure ‘fit for purpose’

16

Generic medicines of special interest

How to ensure robust supply?

Encourage applications …

– Faster evaluation time? – Queue jump?

Case study 1. Medicine shortages Case study 2. Medicine expenditure

17

Consultation Outcomes

… taking a different approach

• Feedback

– Mixed responses … with concerns – No clear benefit for either case study – More efficient TGA processes would be of greater benefit to all – Fast processing of manufacturer changes would assist with medicine shortages

• Outcome

– Consideration of further reform to the variations process for prescription medicines – Applies to all Rx medicines, therefore outside the Generic Medicines Reform Program

18

Next steps …

Targeted consultation

• Revised requirements for use of

an overseas reference product

• New templates for

bioequivalence data

• New process for early advice
• Updated guidance
• Draft templates and guidance
• Confirm key concepts

• The latest on variations
• Generic Medicines Reform Program
• Human cells and tissues regulation (excluded goods)

20

Types of therapeutic goods

Medicines

• prescription medicines
• over-the-counter medicines
• complementary medicines
• blood, blood components and plasma derivatives
• gene therapies

Medical devices

• implants (artificial hips, breast implants)
• in-vitro diagnostics (pregnancy tests, blood glucose monitors)
• low risk medical devices (bandages, tongue depressors, condoms)

Biologicals

• tissue-based products (skin and bone)
• cell-based products (MSCs)
• viable animal cells and organs

2 1

What is an excluded good …

Excluded vs exempt goods

• Excluded

– Not subject to the Therapeutic Goods Act 1989

Not to be confused with…

• Exempt

– Some requirements are not applied

Defined in a legislative instrument

Therapeutic Goods Regulations 1990 Schedule 5 – exempt from being on the ARTG Schedule 7 – exempt from GMP licence

22

Therapeutic Goods (Excluded Goods) Order

• pre 2019

Autologous cells and tissues (Medical practice)

• collected under the care of a medical practitioner
• manufactured for treatment of a single indication
• in a single course of treatment of that patient by the same

medical practitioner, or by a person under their supervision –Not in alignment with most overseas regulators –Multiple concerns with this approach

Review of this position was needed

23

Review of Excluded Goods Order

• Concerns raised with current Order

– Advertising claims for unproven therapies – Scope of activity and complexity of products has changed since 2011; increasing safety concerns – Scope of exclusion is not internationally aligned

• Public consultation on options in 2015 and 2016
• Government agreement to an option supported by the

majority of stakeholders in 2018

• 12 month transition period to allow operators to comply with

the new regulations or cease supplying ended on 1 July 2019.

24

Autologous Human Cells and Tissues

Excluded Goods

• Must be

manufactured and used in an accredited hospital

• Medical or dental

practitioner

Exempt Goods

• Minimally

manipulated and homologous use

• Manufactured and

used outside a hospital

• Medical or dental

practitioner

Full Regulation

• Manufactured and

used outside an accredited hospital

• More than

minimally manipulated, or

• For non-

homologous use

25

• The latest on variations
• Generic Medicines Reform Program
• Human cells and tissues regulation (excluded goods)
• Faecal Microbiota Transplantation

26

Faecal Microbiota Transplantation (FMT)

• Takes faecal material from a healthy individual for transplant to a patient
• Hypothesis: ‘Healthy’ microbiota correct the underlying dysbiosis associated with

disease state

– Fresh, frozen, encapsulated – Varying degrees of processing – Allogenic vs autologous – Stool banks

Donor

• Pre-screened

Processing

• Testing
• Processing
• storage

Patient

• Administered

under medical supervision

27

FMT – a new regulatory challenge

• Medicine or biological?

– Different regulatory requirements – Different safety considerations – Different approaches overseas

• No goods on the Register
• Increasing use within

Australia

• Recognised treatment for

Clostridium difficile infection

UNAPPROVED BIOLOGICAL

28

The Biologicals Framework

Regulated as biologicals

Tissue-based products (skin, bone, ocular, cardiovascular) Cell-based products (T cell therapies, human stem cells) Combined cell and tissue products (collagen matrices for localised cell delivery) Living animal cells, tissues,

• rgans

(xenotransplantation)

Not regulated by the TGA

Fresh viable organs Assisted reproductive technologies (in vitro fertilisation)

Fresh haematopoietic progenitor cells (bone marrow transplants)

Cells and tissues made in an accredited hospital, by a medical or dental practitioner, for autologous use in a single patient under the care of that medical practitioner

Regulated, but not as biologicals

Animal tissue products (non-viable) Biological prescription medicines (vaccines, plasma derivatives) Labile blood and blood components Haematopoietic progenitor cells (non- fresh transplants)

29

Critical considerations …

• Need for GMP
• Infectious disease transmission

– Donor selection and screening – Current TGO 88 – In vitro diagnostic tests

• No advertising of biologicals
• Continued supply for existing

patient groups

• Rapid growth and evolution in

the sector

30

Access to unapproved biologicals

Biologicals that, under the Regulations, are exempt from some requirements Special Access Scheme Authorised prescriber Personal importation For experimental use

31

… for new regulatory scheme

Possible approaches

– Class 1 biologicals? – Alignment with haematopoietic progenitor cells? – Alignment with autologous human cell and tissue products? – Self-regulation?

32

• The latest on variations
• Generic Medicines Reform Program
• Human cells and tissue regulation (excluded goods)
• Faecal Microbiota Transplantation
• 2D DataMatrix codes for medicines

33

Changing regulatory requirements

Overseas

• EU - Falsified Medicines Directive
• India – export requirements
• Track and trace models

– Turkey – Argentina – South Korea …

34

In Australia …

TGO 91 for prescription medicines

–Machine readable code –GTIN and product identifiers

– GS1 Linear barcode or 2D DataMatrix

–Transition ends Sept 2020

How can these requirements align with

• verseas requirements???

35

Wide range

• f

possibilities

36

New Australian standard

Timeline for implementation

• Pre-consultation workshop
• Draft new standard and

supporting documentation

• Public consultation on draft

standard

• Finalisation of standard
• Target date – mid-2020

37

Questions?

38