Presentations from a special SPARK Co-Lab Actuator Series event in partnership with PlusLife, the Perth Bone and Tissue Bank, on Biotherapeutic Manufacturing: from the Bench Lab to the GMP Facility. Learn more about: - What it means to be certified as a GMP facility by the TGA; - The role a GMP facility plays in the commercialisation journey of your therapeutic good (biologicals, medicines & devices); - The history of PlusLife and the opportunities that exist for start-ups and researchers to make use of the new PlusLife facilities.

2. Welcome and Acknowledgement
We respectfully acknowledge the past and present
traditional owners of the land in which we are meeting,
the Whadjuk Nyoongar people.
It is a privilege to be living in Nyoongar country.
We also acknowledge past donors and their families
and celebrate the life they have enabled others to have

3. • Emergency Exit Points
• Evacuation Meeting Point
• Facilities & Amenities

4. What is Jersey Day?
Jersey Day was inspired by the
story of Nathan Gremmo (aged
13), who was tragically lost in
an accident in 2015. Nathan’s
family chose to give the gift of
life to others in honour of
Nathan’s generous personality.
Friday 31 August marks the
fourth annual Jersey Day, a
national community-led
initiative organised by the
Nathan Gremmo
Community Fund dedicated
to spreading the message of
organ and tissue donation
and encouraging more
Australians to register their
donation decision at
www.donatelife.gov.au

5. A Brief History of PlusLife
(Perth Bone and Tissue Bank)
David Toner
(Operations Manager)

6. Who/What is PlusLife?
• PlusLife (Perth Bone and Tissue Bank) is a not-for-profit
organisation, responsible for the retrieval, processing and
distribution of donated human bone & tissue for the
surgical treatment of patients in need.
• We are the state’s only bone bank and have provided
over 25 years uninterrupted service to the health sector.
A Brief History of PlusLife (Perth Bone and Tissue Bank)

7. Tissue Donation
• Unlike organ donation, most people are unaware that tissue
donation is even possible. Yet one single bone & tissue donor
can impact the lives of up to 60 patients.
• Donated bone and tissue (e.g. tendons) are received from
patients undergoing total hip replacements or with the
consent of next of kin, donated after death.
• Processed into graft materials, used for the surgical treatment
of patients with bone cancers, complex joint problems, spinal
deformities; and recently, patients with dental and
maxillofacial bone loss.
A Brief History of PlusLife (Perth Bone and Tissue Bank)

8. Tissue Donation

9. PlusLife – the early years
• PlusLife began live as the Perth Bone & Tissue Bank, Incorporated
in 1992
• Two small freezers were donated by the SCGH Ladies Auxiliary
and were housed in a cottage on the HPH site.
• Two staff (One, who is now our MD and a secretary) were located
on a lab bench in the QE2 Medical Centre in February 1993.
• Seed funding grant ($200k) was received from the Lotteries
Commission of WA to purchase additional freezers and our staff
grew to 3!
• The bank moved to the old laboratory building on the Royal Perth
Rehabilitation Hospital later in 1993.
• During the time at RPRH (until 1997) graft was processed in the
Operating Theatre – all done with borrowed equipment.
A Brief History of PlusLife (Perth Bone and Tissue Bank)

10. PlusLife – building the business
• In 1996 a second $250,000 Lotteries Commission co-
funding grant was received
• Used to refurbish a section of what used to be the artificial
limb factory on the Hollywood Repatriation Hospital site
(now Hollywood Private Hospital).
• Site provided a cleanroom and more space.
• Having the cleanroom enabled the bank to begin to build
the business.
• Obtained its TGA License late 1997
• As the service expanded, staff numbers grew and
eventually outgrew the available space
A Brief History of PlusLife (Perth Bone and Tissue Bank)

11. • The building was subjected to repeated weather
damage, which was a major problem.
• On two separate occasions (notably a hail storm
in March 2010) weather damage caused the
cleanroom system to require major repairs
which took about 3 months
• No interruption to service, but
• A new facility was urgently needed
Facility Troubles
A Brief History of PlusLife (Perth Bone and Tissue Bank)

12. Time to Move on
• By 2015 and after failing on 15 sites, we had been looking for a permanent home
for almost 10 years.
• After first identifying it in 2015, the Midland property (our new site) was finally
secured as a suitable location in 2015.
• A long term lease was negotiated, but there were no funds to build the lab.
– Professional fundraisers engaged,
– advised that philanthropists felt that the Government should fund a building.
– The Government was not eager to agree to this view.
• A political campaign was implemented,
– Significant amount of lobbying
– State Govt allocated $10m in the 2015/2016 Health Budget
– saved PlusLife (actually one month form closure)
A Brief History of PlusLife (Perth Bone and Tissue Bank)

13. Moving on…….
• New site commenced building in November 2016
• Operations remained at Hollywood until the Midland facility
was completed by the end of 2017.
– It took 11 months to complete the building.
– Staged TGA Inspection due to imperative to vacate HPH site
– Took another 5 months before we were fully operational.
– Continued to provide an uninterrupted service.
• It is a privilege to work in this space, allowing us to commit
to providing our service well into the future.
• This new phase of PlusLife provides greater flexibility for the business
– More space
– Research and Development Lab space
– Microbiology lab
– Opportunities for collaboration
A Brief History of PlusLife (Perth Bone and Tissue Bank)

14. 2018 Winner!
Master Builders Excellence
in Construction Awards
A Brief History of PlusLife (Perth Bone and Tissue Bank)

15. What Does it Mean to
be a GMP Facility
John Morri
(Quality & Regulatory Affairs manager)

16. What Does it Mean to be a GMP Facility
You’ve Got a Product.
How Do You Get it to Patients?
Manufacture and supply of Therapeutic goods in Australia is regulated by
the Therapeutic Goods Administration (TGA) under the Therapeutic
Goods Act 1989
To comply with the Act and be able to market a therapeutic good in
Australia 2 of the things you need are:
• Have the product on the Australian Register of Therapeutic Goods
(ARTG)
• Somewhere to make the product

17. What Does it Mean to be a GMP Facility
ARTG Registration
You will prepare a Dossier which will be reviewed by TGA. The Dossier will
include
• Details of what the product is, including packaging and labelling
• Review of literature relevant to the product and its use
• Details of starting materials
• Details of the manufacturing process, including critical control points
• Details of the risk management process used to identify critical parameters
• Details of trials and validation testing from all stages of the product
development cycle used to demonstrate the quality, safety and efficacy of the
product

18. What Does it Mean to be a GMP Facility
Somewhere to Make the Product
A facility used to manufacture therapeutic goods must be licenced by the
TGA
The licence defines what manufacturing steps can be performed at the
site
Manufacturing steps include
• Processing
• Storage
• Testing
• Release for Supply
• Steps performed by outside contractors (e.g irradiation)
Sub-contracting a manufacturing step DOES NOT reduce the
manufacturer’s responsibility for the compliance of that step

19. What Does it Mean to be a GMP Facility
What is required to obtain a
manufacturing licence
The TGA will audit the facility for compliance to the Australian Code of
Good Manufacturing Practice
There are a number of different codes for different therapeutic goods
types
• Medicines
• Blood and Tissues
There are equivalent requirements for devices

20. What Does it Mean to be a GMP Facility
What are the code requirements
The codes of Good Manufacturing Practice have
• Requirements for the people making the product
• Requirements for the facility and equipment being used
• Requirements for documentation
• Requirements for the materials used in the manufacture of the product
• Requirements for product complaints and recalls
• Requirements for the use of computers in the manufacturing process
• Requirements for awareness of what is happening in the industry

21. What Does it Mean to be a GMP Facility
Requirements for people
• The organisation structure must demonstrate independence of the
quality function from the production function
• There must be sufficient staff to complete the tasks required to make
the product
• The staff must be shown to be competent in the performance of their
assigned tasks

22. What Does it Mean to be a GMP Facility
Requirements for the Facility
and Equipment
• The facility must be in an appropriate location
• The design and layout should aim to minimise the opportunities for errors to occur
• Materials of construction must be appropriate to the product being produced
• The facility needs to be easily cleanable
• The facility must be able to maintain appropriate conditions for the manufacture and
storage of the product
• There must be qualification records to demonstrate that the facility and equipment meets
the specified requirements over the entire range of expected operating conditions
• There must be contingencies in place to protect the product

23. What Does it Mean to be a GMP Facility
Requirements for Documentation
• All processes need to be documented (Standard Operating
Procedures)
• The documentation needs to be controlled
• All activities need to be recorded
• Any change to a record must leave the original entry legible
• Records need to retained according to a schedule
• Records need to demonstrate traceability from starting materials to
issued product

24. What Does it Mean to be a GMP Facility
Requirements for Materials
(including donors)
• Materials must be defined in specifications
• Materials need to be assessed for compliance to the specification
before being accepted for manufacture
• Suppliers should be qualified to ensure their ability to supply material
meeting requirements

25. What Does it Mean to be a GMP Facility
Other Requirements
• The manufacturer must have a system for dealing with complaints and
recalls
• Any changes must be made in a planned and controlled manner
• The manufacturer must have a system for keeping themselves
informed as to developments in their industry (biovigilance,
pharmacovigilance)
• Use of computers and apps is acceptable, but the requirements of the
code still apply and must be demonstrated

26. Dr Felix Yao
(University of Western Australia)
PlusLife –
Research and Development

27. The Lay of the Land

28. - Biotechnology represents an area of business that provides opportunity to turn our nation’s economic
fortunes around
- Australia produce world-class research, but we have trouble transferring our research into economic gain
- Modest growth of 3.1% the past 10 years
(vs. worldwide growth rate of 10% in the same period)
- Worldwide net income from Biotech outpaced Australia’s by 220%
- Competitive race – currently Australia holds the upper hand in quality research outputs and a highly
educated workforce, but need to be savvy about targeting our investments to areas that most need them
- This is an industry that cannot afford complacency
PlusLife – Research and Development
FOREWORD

29. PlusLife – Research and Development
BIOTECH in Australia
- OECD definition = application of science and technology to living organisms in order to alter living and non-
living materials for the generation of knowledge and development of products and services
- Sector expected to grow at a rate of 4.4% a year until 2021
- Most Australian biotechnology companies are research-intensive small to medium-sized enterprises
operating in the start-up or growing/expansion phase.
- These mostly comprise of spin-offs from universities and other research organisations.
- Australia’s biotech industry is being outperformed
- Industry growth 3% vs. 10% worldwide
- Revenue growth 9% vs. 24%
- Employment growth 8% vs. 9%
- Net income growth 11% vs. 231%

30. PlusLife – Research and Development
RESEARCH in Australia
- Australia is a substantial global contributor of fundamental research:
- Comparatively large contribution of 3% of the world’s research publications achieved with only 0.3% of the global
population
- Ranks 5th in terms of the number of publications in top journals per 1,000 population ahead of the UK, United
States, France, and Germany, but behind smaller Scandinavian countries
- Citation rates are world class, ranking higher than most of our major competitors
- Significant proportion from CSIRO which ranks in top 1% of the world’s scientific institutions.
- 5th ranked nation amongst the world’s top 200 universities.
- Still spends less on R&D expenditure than the OECD in terms of both gross and business expenditure
measures.
- Consistently perform below average on the experimental development indicator of R&D

31. PlusLife – Research and Development
Innovation POTENTIAL
- Skilled workforce: Australia ranks 4th in proportion of PhD graduates in life sciences per million population,
behind the United Kingdom and Canada (tied in 2nd place) but ahead of the United States, France and
Germany.
- The Australian Bureau of Statistics (ABS) reported business expenditure on R&D in biotechnology as
$180m for the 2016-2017 period, representing 1% of the total business expenditure on R&D during that
period
- There is a significant gap on biotechnology-related R&D between Australia and the rest of the world. In the
same period the United States spent $30b, France $6b, Germany $2b, and Canada $500m.
- i.e., The Australian biotechnology industry spends less than 0.5% of the US biotechnology R&D total
expenditure (about 12 x per head of population)
- R&D expenditure is a key contributor to a nation’s productivity, and is indicative of competitiveness and
GDP growth for the future

32. PlusLife – Research and Development
Research collaboration with firms
- Australia relies on our public institutions to conduct R&D (universities and the CSIRO)
- Ranks 32nd out of 33 OECD countries for research institution to industry collaboration with small and medium sized
businesses
- And last for collaboration with large companies
- The problem with this reliance is that we are also lacking our ability to create linkages between industry
and research.
- While many Australian universities have created their own Technology Transfer Offices, these have
experienced varied levels of success.
- Collaboration between research and higher education institutions and industry is imperative to the process
of commercialisation of research.

33. What’s a tissue bank?

34. - In Australia there are 9 musculoskeletal tissue banks
(publicly-funded, part publicly-funded, private not-for-profit banks, and private for-profit providers)
- Tissue Banks collect donated human tissue, process and store these tissues and then distribute them to
clinicians for surgical use.
- Live donor femoral heads from hip replacement patients
- All deceased donor tissue banks are supported by DonateLife
- Multiple uses: orthopaedic / spinal / plastic / reconstructive / dental
- Donated tissue may be used for R&D purposes where consent is obtained
PlusLife – Research and Development
Tissue Banking

35. - State and Territory governments who have policy and statutory responsibilities for tissue banking under
their respective legislative regimes
- Safety and quality regulated by the Therapeutic Goods Administration (TGA)
- Financial framework under the Private health Insurance (PHI) scheme
- Not for profit - reliance on reimbursement and grants
- The States provide the legislative Human Tissue Act Framework which broadly states
- there will be no trade in human tissue, and
- provides for the retrieval of tissue for banking with appropriate consent
PlusLife – Research and Development
Tissue Banking: Governance

36. PlusLife – Research and Development
Translational Research
- NHMRC definition: an approach that aims to make medical research findings usable and applicable to
patients without delay. Translational research can be:
- T1: integrated laboratory and clinical research – “bench to bedside” and “bedside to bench”
- T2: exploring ways of applying evidence-based medicine, recommendations or guidelines to clinical
practice.
- PlusLife Research and Development Strategy
- T1: Newer technologies and allografts identified by stakeholders including demineralised bone matrix
and bone gel.
In the longer term, 3D printing (“bioprinting”) is expected to provide fit-for-purpose grafts for bone,
tumour and spinal implantations for reconstructive surgical and dental procedures.
- T2: use evidence-based measures to contribute to outcomes across the business, from donor
recruitment to patient safety.

37. PlusLife – Research and Development
PlusLife Research
R&D Laboratory
- Floorspace: 60m2
- Cleanroom: (ISO 5 capability)
- Separate access controls
LotteryWest grant:
- $250,000
- Equipment
R&D Micro Processing

38. THANK YOU!