Future perspectives on pharmaceutical capsule product manufacturing. Sven Stegemann CPhI St. Petersburg April 16, 2014

Transcription

1 Future perspectives on pharmaceutical capsule product manufacturing Sven Stegemann CPhI St. Petersburg April 16, 2014

2 Introduction "The most reliable way to anticipate the future is by understanding the present." Megatrends. John Naisbitt 1982

3 Introduction GlaxoSmithKline CEO Andrew Witty cautioned that the pharmaceutical industry must be open to change in order to tackle issues such as affordability, access, escalating research costs and declining productivity, instead of relying on "25-year old" models Sven from Capsugel says: He is right!

4 Understanding the present

5 R&D productivity More than 600 drug launched in the past 20 years 600 We set high therapeutic standards and best in class drugs We made effective therapies available for most of the simple diseases N of Drugs While we start to understand disease biology drug therapies are getting either personalized or combined as multi-target therapies Stegemann et al Eur J Pharm Sci 2011

6 Emerging Markets Expenditure on health grew between from 2.6 to 5.1 I$ trillion I$ = International dollar. Comparative currency defined by the Worldbank x 3 mature market size Health economies (2008) Low-expenditure Rapid growth expenditures High- expenditure People 2.6 bio 2.9 bio 1.0 bio Spending / capita 103 I$ + 5.8% 413 I$ + 8.1% 3752 I$ + 5.5% 6 WHO Primary Health care report 2008

7 Anticipate the future

8 Patient centric drug products

9 Patient centric drug products The patient population : opportunity or threat? Patient centric drug products Patient centric drug products The Agency will undertake specific efforts to ensure that the needs of older people are taken into account in the development and evaluation of new medicines. [EMA Geriatric Medicine Strategy - EMA/CHMP/137793/2011]

10 Patient centric drug products Older adults are Main medicinal product user group Most heterogeneous patient population The critical aspects of drug therapy in older adults (beyond geriatrics) Polypharmacy Visual Cognitive Auditory Motoric Swallowing Adherence The Geriatric Medicine Society is actively involved in geriatric medicines (

11 % blind / visual impaired Patient centric drug products Visual impairments and poor vision are common in elderly. As the most important sensory organ this might impact the drug therapy Polypharmacy is common among older adults increasing the challenge of product identification Poor visual acuity Good visual acuity Klaver et al 1998, Stegemann 2005 Age

12 Patient centric drug products Swallowing issues Frequency in patients aged 70 years and older (254 patient randomly selected from primary care) 27.2 % Prevalence of signs of dysphagia 20.5 % Impaired efficacy of swallowing 15.4 % Impaired safety of swallowing 6.7 % Aspiration One third of patients in long term care facilities experience serious difficulties with swallowing solid oral dosage forms (SODF) Crushing or modifying dosage form Omit taking the drug Internet search identified 66 different devices offered! Serra-Prat et al JAGS (2011); Stegemann et al Int J Pharm (2012)

13 Case study Develop enhanced packaging for sprinkle products Hypothesis Multiparticulates and minitablets show evidence of ease of swallowing (pediatric, geriatric, dysphagia) Easy of different dose strength provision using multiparticulates and minitablets (especially for MR) Flexibility in FDC development and manufacturing Basic concept: Swallow as a single unit or open and disperse in food/beverages

14 Case study Proof of concept in Patient/Care Givers Results 90 % of the volunteers opened the capsule in a horizontal position and 10 % in a vertical position Sprinkle capsule design 2 better then design 1 Sprinkle capsule design 2 confirmed by 81% of participants to be very easy or easy to open Standard Coni-Snap only 29% of participants evaluated as very easy or easy Very easy Easy Somewhat easy Difficult Very difficult Perceived ease of opening of Sprinkle capsule design 2 versus standard Coni Snap capsules 20 0 Sprinkle Design Coni-snap Design

15 Sprinkle formulation Depakote capsules (divalproex sodium) for use in specific patient populations Depakote sprinkle capsules may be swallowed whole or the contents may be sprinkled on soft food. Creon capsules (pankrelipase) if you or your child can t swallow If you have trouble swallowing capsules, you can add the capsule contents directly onto certain foods such as applesauce. 21

16 Sprinkle formulation Dual release Proton pump inhibitors are frequently if not routinely used in older adults Patient centric design in three aspects: 1. Dual release & once daily 2. Sprinkle option 3. Pre- or postprandial Take with or without food Unlike some medicines, which should be taken on an empty stomach, you can take DEXILANT with or without food. Capsules should be swallowed whole, or they can be opened, sprinkled on one tablespoon of applesauce, and swallowed right away. As with other medications, be sure to take DEXILANT exactly as it was prescribed and for the full length of time.

17 Manufacturing efficiency

18 Manufacturing efficiency Cost structure of pharmaceutical manufacturing per unit operation GMP space Number of surrounded equipment Energy Solvent/water/detergence HVAC Validation/qualification QA/QC/QbD Operators/planning Cleaning/waste Maintenance Yield losses Inventory/JIT implication Depreciation Equipment effectiveness (utilization time) Safety stocks Mainly related to drug substance St. Gallen report 2006

19 Manufacturing efficiency Cost structure of pharmaceutical manufacturing per unit operation GMP space Number of surrounded equipment Energy Solvent/water/detergence HVAC Validation/qualification QA/QC/QbD Operators/planning Cleaning/waste Maintenance Yield losses Inventory/JIT implication Depreciation Equipment effectiveness (utilization time) Safety stocks Mainly related to drug substance St. Gallen report 2006

20 Manufacturing efficiency 26 Trout & Bisson 2009

21 Manufacturing efficiency Batch process Continuous process The various immediate-release oral pharmaceutical forms shall be Considered to be one and the same pharmaceutical form. Directive 2004/27/EC Art 10(2) 27

22 Manufacturing efficiency differentiation Capsule types Capsule sizes Capsule Colors Capsule imprints 5 13 > 6000 endless Coni Snap Vcaps Plus Vcaps DRcaps Plantcaps el 00 0el 0 1el 1 2el 2 3 4el

23 29 Conclusions

24 Conclusions The healthcare market is undergoing a significant change which is challenging our 25 years old business model Thanks to this dynamics there are huge opportunities for innovations Increase adherence and therapeutic outcomes Provision of affordable medicines in emerging markets Serve geriatric patient population Move from efficacy to effectiveness Manufacturing efficiency and patient centric drug products will play a key role in the future healthcare provision in mature and emerging markets 30

25 Sven Stegemann, PhD CAPSUGEL Director Pharmaceutical Business Development Rijksweg 11 B 2880 Bornem Belgium phone: sven.stegemann@capsugel.com Geriatric Medicine Society e.v. President D Aachen Germany phone: info@geriatric-medicine.org