Your micronisation and milling partner

Transcription

1 Your micronisation and milling partner

2 Micronisation of Active Pharmaceutical Ingredients -Industrial Approach- 2/36

3 - Founding year: Owner-managed company - Many years of experience - Micronisation and refining of your pharmaceutical products - Micronisation under aseptic conditions - Blending - Sieving - Processing of quantites from a few grams to tons - Labservices for Particle-Size-Distribution - Highest quality and safety standards - Various certifications and approvals (GMP certificate, manufacturing authorization, FDA authorization, accreditation in Japan) - Trained employees - Global customers 3/36

4 Organigram Manager Organisation and Planning (IT) A. Rasack Technical Department M. Bertschuk Operations Manager Dr. S. Sehlmeyer T. Schrage Production Manager T. Schrage B. Frese Operators Production Trainees / Apprentices Managing Director A. Rasack Qualified Person Dr. M. Sotoodeh Dr. S. Sehlmeyer Head of Administration A. Rasack Manager Quality Assurance M. Franzke P. Stroncik Warehousing and Shipping A. Bechtold Trainees / Apprentices Office Manager N. Bolte Employees Quality Assurance Employees Administration / Office Trainees / Apprentices Operators Quality Control Manager Quality Control Dr. M. Sotoodeh B. Tetzlaff E. Schultz Operators Monitoring + Microbiology You may meet us at booth 211F40 Facility Manager M. Bertschuk Operators Safety, Health and Environment (SHE) 4/36

5 Advantages: - the economical impact - controlled and reliabel PSD - controlled release better to achieve

6 We deliver all over the World 5/36

7 Statement- (Chemist`s- wishful thinking) Milling and micronization is an additional step with a significant contribution to our drug substance production costs. There must be a way to eliminate this step by cristallization to meet particle size specification. You may meet us at booth 211F40 6/36

8 Statement- (pharmaceutical production ) If our API producer ask us regarding particle size distribution, we don t care too much for the specified numbers, we take them for granted. We want and we need to have the very same particle size distribution like the delivery before. Generally, the cristalization step is not capable to deliver repeatable and consistant particle size in long term. 7/36

9 Milling: (50µm) Defined internally Micronisation: (10µm) Defined internally 8/36

10 Development Chemist`s Priority: For ease of crystalisation,separation and drying suitable Crystals are produced 9/36

11 In the past the need for controlled particle size in a narrow range was by far not as important. Why? 10/36

12 Development of Pharmaceutical Technology From a tablet to a multilayer micro pill 11/36

13 Digoxin In the 1970s, a US supplier changed his source of digoxin in their tablets.the drug`s particle size distribution was finer. The result was several deaths. Particle size influence the speed of transmitting and the delivered quantity! 12/36

14 One of the new challenges facing the pharmaceutical production is to satisfy the call for controlled release of API`s bio availability, solubility time / place of dissolution / controlled release / slow, fast, location stomach acid neutral basic exit micro pills with multi layers Inhalation better content uniformity 13/36

15 To make this kind of formulation work the need for controlled and reliable particle size distribution is essential. If this is not the case, the losses of API while producing multi -layer micro pills are exorbitant. 14/36

16 Within the pharmaceutical development and scale up phase of one of our major drug products, the loss of API went down from 60% to less than 20% related to the narrow range of particle size distribution. 15/36

17 Milling and micronisation of DS can be regarded as the most generally applicable approach to control particle size (distribution) concerning typical pharmaceutical requirements. 16/36

18 Scale up Strategy Only Exceptions Development Production Preferred route Small volume Big volume PEG mill PEG mill Große Stiftmühle Not preferred Mechanical milling Impact mill Impact mill Impact mill preferred Spiral jet mill Spiral jet mill Spiral jet mill preferred Micronisation Fluidised bed opposed jet mill Fluidised bed opposed jet mill Fluidised bed opposed jet mill preferred 17/36

19 The selection of milling and micronisation method takes place in an early development phase. Changes in an advanced stage of development causes major set backs for the pharmaceutical development. The presence of identical technology in development and production has to be secured by investment. Focusing on the most flexible and available milling and micronisation technologies. Exceptions need to have a major reason. 18/36

20 Milling and Micronizing Process Late LO Predev. Phase I Phase II Phase III LOM IRC DC IDC IDC IDC Milling & Micronizing Process Evaluation/ Feasibility T-DS / Technology Selection M&M Process Development Scale Up/Transfer Process Validation Production Primary Stability Batches Market Supply 19/36

21 Scale-up AFG R&D Lab Pilot Production PICOLINE AS 40 AFG 100 AFG 200 1g- 500g define PSD Pre selection of technology 0,5 100 kg selection of technology kg specification PSD evaluation & validation solid properties 20/36

22 Scale-up AS R&D Lab Pilot Production AS 33 AS 50 AS 100 AS 200 AS g 20 g define PSD Pre-selection of technology 20 g 200 g selection of technology 200 g 1 kg specification PSD evaluation 1 kg 200 kg validation 200 kg tons validation solid properties 21/36

23 What does it look like? 22/36

24 Fluidised bed opposed jet mill 24/36

25 Fluidised bed opposed jet mill Hosokawa Alpine AFG 100 Hosokawa Alpine AFG /36

26 Spiral Jet Mill AS /36

27 Impact Mill Authorized by Hosokava - Alpine 26/36

28 Process monitoring (PM) particle size distribution Before milling Running process After milling 28/36

29 before milling 29/36

30 After milling 30/36

31 before milling 31/36

32 After milling 32/36

33 Where are we today: The need of milling and micronisation is not discussed anymore Same drug substance, same PSD PSD specifications for all our drug substances Close working relationship between pharma production and milling and micronisation High awareness regarding economic impact 33/36

34 2018/2019 On an area of more than 2000m² we are developing one division for cephalosporins and one division for penicillins

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36 A multimillion $ investment in a modern and state of the art plant is one step. Well educated and trained employees are essential to run the plant succesfull. Otherwise the invested money is wasted! 34/36

37 Continuous Improvement Quality Improvement Process Corrective Action Preventive Action Move from Corrective to Preventive Action We Take Quality Personally 35/36

38 Thank you for your attention 36/36