Hightech Contract Manufacturing Medical B.V.

The start of a new innovative company in Nijmegen!

Company History(The initial idea)

Setup a Contract Manufacturing Organization for the development and

production of biological implants and devices based on human as well as

animal tissue.

Be an extension of Customers policy and business in the development and

production process.

Be a service provider in installation of technologies and production

processes at Customer Sites, globally.

Founders History

Biochemists with experience in (Contract) Manufacturing of Medical

Devices, Pharmaceuticals and Tissue Constructs.

Advising and supporting companies on operational, quality and regulatory

matters.

Extensive international network.

Complementary characters but share being independent, targeted and the

passion for water.

HCM-Medical Facilities (Kerkenbos 10113, Nijmegen)

Company History(The Action Plan)

2014

August : Decision to start CMO

November : Registration of HCM-Medical B.V.

2015

February : Selection of Facilities

March : Start setup Business Plan

April-July : Investor selection and presentation

October : Investment process (almost) completed

November : Clean room construction started

December : Manager Production hired

2016

January : Clean room construction completed

First Customer contract signed

April : Offical Opening of HCM-Medical

First Inspection by Notified Body for CE License

HCM-Medical

Business PlanCompany Vision

Development and production of niche products for third

parties whereby through new technologies solutions are

provided for faster healing of the patient with oncological

applications as an important priority.

Business PlanCompany Mission

HCM-Medical BV, is a contract manufacturer that in close collaboration with thecustomer develops products and implements technologies for the purpose of manufacturing unique and hightech medical products.

Driven by technology Focus on medical implants with unique proporties for niche applications. High level of customer satisfaction supported by added services:

- Product Development- Validation and Registration

Business PlanHCM-Medical Business

HCM Medical: a contract manufacturing company

HCM Medical, also known as Hightech Contract Manufacturing Medical, is a

contract manufacturing organization that develops and manufactures products and implements technologies.

The purpose of the production is to develop and manufacture unique and

high-tech medical products for various medical applications which include

cardiovascular, urological, dermatological, dental, ophthalmological and orthopedic applications.

At the same time, HCM Medical will put an emphasis on the need for tissue products required in tumor surgery, development and production of tumor

vaccines and the development of drug-release products for local treatment by implantation.

Business PlanHCM-Medical CMO Services

Products or servicesHCM-Medical can provide the following services:

Production of products for customer within the current licenses, suchas: Medical Devices Pharmaceuticals Tissue (human)

Develop new products, in collaboration with the customer, within the possibilities and expertise

Produce, on behalf of the customer, the first batches after product development, for clinical studies or product registration

Provide knowledge in the field of test method developmentProduct (process) validationProduct registration

Business PlanHCM-Medical Technologies

HCM Technologies

Together with customers HCM Medical will specialize in developing and producing

products that have a biological origin; either the processing of human and animal tissues to new implants as well the purification of biological materials such

as collagen for the production of high quality implants.

Technologies performed by HCM Medical, such as: Supercritical CO2 for the purpose of removal of cells and

other unwanted materials from tissues.

Freeze-drying for the purpose of production of tissue constructs Continuous improvement of existing technologies and

introduction of new techniques: Electro-spinning, 3D printing, etc. Aseptic preparations; both formulating and filling under controlled

aseptic conditions.

HCM-Medical Investors

2 Founders of HCM-Medical

Private Investor (Shareholder)

Rabobank (Overheidsborgstelling)

Mibiton (Financial lease equipment)

Gelderland voor Innovatie (Innovation loan)

Clean rooms

Equipment

Working Capital

750K

HCM-Medical Facilities

HCM-Medical Facilities

HCM-Medical Facilities

Products and Technologies

Supercritical CO2 technology (Extraction & Impregnation)

scCO2 Products and Technologies

Processing

Cleaning

Supercritical CO2technology

overcomes theshortcomings of tradional tissue

processing

Drying

Drying of tissueconstructs as

alternative forfreeze drying

CoatingImpregnation

Impregnation andcoating of

antibiotics andAPIs

Sterilization

scCO2 sterilization for the purpose of

new product development

Musculoskeletal tissue

Bone flaps

Femoral Heads (Cancellous)

Sternum

Cortical bone& Tendon

Mandibula

Vertebra

Soft Tissue

Trachea

Heart valves& Pericard patches

Blood vessels& Aorta patches

SkinUrethra

Amniotic membrane

Tissue source

Product & Technology Development

Grants for technology & product development

Heart valves

scCO2 sterilization

scCO2 equipment development

Grants

(approved)

Business partners & New customers

Business collaborationsCustomers

Conclusion

Challenges:

Investment (will we find the required amount?)

Customers (will customers sign contracts?)

Successfactors and Pitfalls:

Network (former contacts bring equipment, contracts, new businesses, employees etc.)

Leadtime of investment process (6-10 months)

Decision on Investorselection (conditions of investors)

Dos and Donts:

Write a readable Business Plan

Invest in the necessary (no unnecessary decoration)

Select appropriate facility (dedicated to the business and logistics)

Hightech Contract Manufacturing Medical B.V.

Kerkenbos 10113

6546 BJ Nijmegen

www.hcm-medical.com

024-206 2971

Products and Technologies

Products

Tissues Cleaning of human and animal tissues for the purpose of tissue reconstruction in orthopaedics, dental,

cardiovascular, dermatology, trauma, urological, etc. applications.

Biological molecules Purification of collagen from animal tissue and production of collagen products & constructs for

multiple applications.

Licenses required: 1. HumanTissue license (IGZ)2. ISO13485 MedDev (Notified Body)

Products and TechnologiesSupercritical CO 2 as virus inactivation technique for bone; a mild way of processing. Bokhorst A.G 1, Al B2, Valster H3 1De Oude Gracht Groep 2 Sanquin Blood Supply 3 EMCM b.v.

Microbiological safety of bone allografts remains a significant concern. Many of the current processing methods to reduce the risk of transmission alter the structure and characteristics of bone. The Supercritical CO2 fluid technique is used in tissue banking as an alternative sterilization technique because of its cleaning and bactericidal capacities, while maintaining the natural structure of the tissue. Aim of this study is to investigate the capacity of this ScCO2 processing method for bone to inactive viruses as well Materials & Method Untreated cortical and cancellous bone particles ( 5 samples each) were spiked with different viruses representing the critical virus groups, and processed with the following steps :: ScCO2 extraction of debris, H2O2 30% washing step and NaOH 2M for prion inactivation. After each step the viral removing or inactivating capacity was determined. Results

Results of the validation studies [CF (log10 95% CL)]

Treatment

Supercritical H2O2 NaOH Minimal

fluid 30% 2M Overall

CO2 (2 hrs at 40C) (1 hr at 20C) Virus

Virus extraction Reduction

BVDV 3.8 0.4 > 5.2 0.2 > 6.7 0.2 > 15,7

CPV 0.5 0.4 > 4.7 0.3 > 5.7 0.3 > 10,4

HAV 0.9 0.4 > 3.7 0.2 > 4.9 0.2 8,6

HIV > 6.4 0.2 > 3.7 0.3 > 5.6 0.3 > 15,7

PSR > 5.7 0.2 > 4.7 0.2 > 7.1 0.2 > 17,5

Minimal overall virus reduction of the SCCO2, H2O2,and NaOH of human bone.

Conclusion:

The processing of human bone with scCO2, H2O2 and Na OH results in a theoretical virus reduction of minimum > 8,6.log 10 A processing method based on ScCO2 completely inactive viruses, which makes it a valuable alternative to other more aggressive inactivation techniques.

Products and Technologies

The supercritical processSterilization

Benefits of Using Supercritical CO2 Sterilization Low temperature and moderate pressure

- Ideal for sensitive organic materials or highly reactive materials Non-toxic (1)

- Compatible with allografts as well as xenografts tissue Able to penetrate to the interior of porous materials

- Reaches pathogens located within the cortex Good solvent capacity for lipids (1)

- Ideal lipid extractor- Improved tissue cleaning

Additive in sublethal dose (25-100 ppm) + scCO2 = synergistic effect and SAL6sterilization

Allows for Terminal sterilization (sterilization in final packaging)

1. Fages J, Marty A, Delga C, Condoret JS, Combes D, Frayssinet P. Use of supercritical CO2 forbone delipidation. Biomaterials. 1994;15:650-656.

Supercritical tissue application(an example)