Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Trainings and much more... Herwig Reichl Hämosan Life Science Services GmbH

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Hämosan LSS: Life Science Services Worldwide services for Pharma and Biotech Hämosan is: Hämosan MmQ: Management mit Qualität Coaching Consulting Training

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: MmQ Coaching – Consulting – Training Strategy Strategic HRM Leadership Managing Creativity Innovation Development

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: HÄMOSAN LSS Viral Safety – QM – Cleanroom Protein purification Viral & prion safety GMP expertise Cleanrooms for Training QM for SMEs, pharmacies etc. –ISO 9001 –ISO 13485

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Our core competence in Hämosan LSS: Safety of Blood Products

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: The Need for Safer Products Long history of transmission of bacterial, viral and recently also: prion diseases via blood-derived therapeutics, vaccines, food etc.: Listeria, Salmonella, SV40, HIV, Hepatitis, Parvo B19, vCJD…

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: 3 ways to improve safety Screening –is not enough ( log reduction): “diagnostic window“ unknown viruses Testing of end product ( log): –lacks sensitivity; unknown viruses Removal and inactivation steps in manufacturing processes! (> log)

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Validated removal and inactivation steps are required for registration by FDA (USA) EMEA (EU) and all other national authorities Consensus: Several (>2) robust steps capable of removing > 4 logs of infectivity each; Validated with several relevant virus models

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: How is it done? 1.Identify possible removal steps in the existing process – if needed, add dedicated ones! 2.Scale down the steps and validate scale-down! 3.Perform validation experiments in safety labs by adding (“spiking“) infectivity and analysing all fractions for it

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Ad 1.: Identification of steps Candidates: Chromatography (AEC!) Heat (wet, dry) Low or high pH Precipitation steps, depth filtration Dedicated steps: Solvent/Detergent treatment Virus (Nano-) Filtration Irradiation (UV, Gamma)

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Ad 2.+3.: Example of a scale- down for process validation: Lab scale: Add 9 ml spike to 81 ml solution; Filtration time: same as at process scale Flow rate per cm²: identical Validate scale-down by comparing products Test all 3 fractions for infectivity! 9000 liter solution Filter 3,6 cm² Filter press: Filter area = 36 m² 9000 liter filtrate Filtercake = waste pump 81 ml 9 90 ml filtrate filtercake pump 90 ml

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Our experience in the field: Scale down validation for all COHN plasma fractionation steps of client Coordinating 4 EU funded research projects focusing on TSE validation 160 virus and prion validation studies for various clients, mainly in blood industry QM and GMP consultancy mainly in (hospital) pharmacies, biotech industry Cleanrooms for practical training (“hands on“!) and pilot scale production (for clinical trials)

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Cleanrooms for training

Hämosan ® Life Science Services GmbH A-8262 Ilz, Neudorf 41 Tel. +43 (0) 3385/8117 mail: Contact: Herwig Reichl Hämosan LSS GmbH Neudorf 41 A-8262 Ilz, Austria