Services

Prague Scientific offers services across different areas in Development, Regulatory and Pharmacovigilance. Our experts allow you to achieve outstanding results within short timelines.

  • We work with the clients through dedicated, cross functional teams which allows us to adjust each project to customer needs
  • Our experience has been built for decades and our teams are best in class in Europe
  • Our focus is to be compliant with all current regulations and future requirements to ensure successful and sustainable project deliveries

API Development

Preformulation

Formulation Development

Value Added Medicines

Analytical Development

Biopharmacy

Clinical Development

Regulatory and Pharmacovigilance

Governance

Nitrosamine Overview

Additional Focused Activities

In response to nitrosamines present in pharmaceutical products, the European Medicines Agency (EMA) and the US Food and Drug Administration (US FDA) have published requirements and limits related to nitrosamine contaminants. Aligned with the recommendations, Zentiva has developed and validated multiple methods to determine concentrations of nitrosamines in pharmaceutical products. As a result, we are able to identify nitrosamine-formation pathways and offer low-nitrosamine APIs, but also pharmaceutical products. Our experience goes far beyond N-Nitroso-N,N-dimethylamine (NDMA) determination, as we already have practical experience with Seventeen nitrosamines, including nitrosamine analogues, as well as with low-nitrosamines Metformin (WO2022079287A1).

All this confirms the versatility and adaptability of our methodology.
As a result, we are able to identify nitrosamine-formation pathways and offer low-nitrosamine APIs, but also pharmaceutical products.

Partnership for success

The Parc

The Parc is a pharmaceutical research platform offering a post-graduate program that is based on collaboration between academic and industrial partners (https://www.theparc.eu). At The Parc we want to build an environment for creative and talented students who will be able to solve current and future challenges of pharmaceutical research. Master and doctoral students work under joined supervision of academic leaders and industrial scientists. In The Parc you will gain theoretical knowledge and practical skills for your future professional career”.

API Development

Route Scouting Services

  • Literature search to establish current state of the art routes, as well as to identify synthetic routes options including designing novel routes
  • Laboratory assessment and optimization in a small scale to select the most promising synthetic route including preparation of standards of impurities
  • Synthesis of oligonucleotides
  • Equipment available: Over 60 fume hoods and laminar flow boxes, Isolator for High Potent Actives (HPAPI) handling, wide range of Reactors with volumes ranging 0,1-20L, Autoclaves for pressurized reactions and hydrogenations

Process Development and GMP Operations

  • Optimization of chemical reactions parameters utilizing Design of Experiments (DoE) and Quality by Design (QbD) principles (e.g. Cost of goods manufacturing, yield, cycle time, quality etc.)
  • Process safety data measurement
  • Designing scale-up and scale-down models
  • Process validation of Development APIs for clinical trials and commercial supply
  • Manufacturing of commercial APIs in the Prague kilolab, Ankleshwar (India) Pilot plant
  • Equipment available: Reactors 25-2500L, Autoclaves 20-630L, Isolation and Drying Units, Sieving and Milling equipment, Spray Dryer

Solid Form Screening and Analytical Development

  • Screening and process development of crystalline forms (polymorphs, hydrates, solvates, salts, cocrystals)
  • Screening and process development of amorphous forms (amorphous APIs, co-amorphs and solid solutions by precipitation, hot melt extrusion (HME) or spray-drying)
  • Particle size modification, API solubility increase systems
  • Analytical method development, Validation and transfer
  • Specification setting, Stability and Stress testing
  • Preparation of CMC part of a Active substance master file (ASMF)

Preformulation

API and Powder Characterization

  • Physical and chemical stability, solubility and dissolution behavior (Intrinsic solubility)
  • Basic phys-chem properties: pKa, log P, (Sirius T3 inForm), Hygroscopicity, Melting Point, TGA
  • Solid form characterization: X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry, solid state nuclear magnetic resonance
  • Particle size characterization: laser diffraction, optical microscopy, focused beam reflectance measurement
  • Characterization of bulk powder properties and optimization of tablet composition based on powder rheology
  • Troubleshooting and investigation of tablet hardening, softening, poor tablet disintegration, chemical degradation and solid form conversion
  • Powder bulk and surface properties: powder rheometer, inverse gas chromatography, drop shape analyzer
  • Water absorption: dynamic water sorption, thermo-gravimetric analysis

Reference product Characterization

  • Reverse engineering of pharmaceutical solid dosage form product and investigation of key characteristics (e.g., stabilization, API particle size distribution) using Raman mapping, scanning electron microscopy, hot-stage microscopy
  • Tablet disintegration: disintegration tester, texture analyzer

Formulation Development

Excipients and Process Selection

  • Drug to Excipient compatibility studies
  • Process selection including Wet granulation, Dry granulation, Direct compression, Fluid Bed Pellet Processing etc

Drug Delivery Dosage Form

  • Solid Oral Tablets/Capsules- Immediate release, Modified release, delayed release, Multi unit delivery systems (Pellets)
  • Oral-Suspensions, solutions
  • Injections-Solutions, Suspensions

Technology

  • Direct compression, Encapsulation, Dry granulation, Wet granulation , Wurster coating, Spray Drying, Hot melt extrusion, 3D Printing, Bi-Layer tablets, Coating
  • Can handle Non-Cytotoxic Oncology OEB 1,2,3 and 4
  • Equipped with Laboratory scale to Pilot scale to Commercial scale batch manufacturing with same design
  • GMP/Clinical batch manufacturing and release
  • Process validation/Qualification and ICH Stability in all Zones
  • Packaging (blisters) including nitrogen atmosphere
  • Injectable ampoule/vial filling line under Nitrogen atmosphere
  • Preparation of CMC part of a dossier

Value Added Medicines

Innovation at Zentiva is focused on identifying currently unmet patient needs, providing missing solutions in the form of value-added medicines (VAMs). Our evaluations are carried in a multidimensional way, providing medical and commercial aspects of value adding, using digital innovation segments to identify what patients are currently missing. More detailed review of our activities is given in the enclosed video.

RIVAROXABAN Capsules – food independent Capsules

RIVAROXABAN Oral Suspension - Patient with swallowing difficulties

ROSUVASTATIN Film coated tablets 15 and 30 mg - missing strengths

DASATINIB Film-coated Tablets – can be given with PPI’s (pH independent absorption)

IBUPROFEN IR + SR Tablets

CANDESARTAN + INDAPAMIDE Film-coated Tablets

BISOPROLOL Solution - Patient with swallowing difficulties

OMEPRAZOLE Rapid Relief Capsules- Faster Onset of action

LORAZEPAM Tablets 0.5mg- For patients with impaired renal or hepatic function

S-AMLODIPINE (Levoamlodipine) Tablets - Lowering side effects

METAMIZOLE + TRAMADOL Film-coated Tablets

DEXIBUPROFEN Film-coated Tablets

AMLODIPINE 2.5mg Film-coated Tablets

SERTRALINE 25mg Film-coated Tablets

VALSARTAN LOW-DOSE (Supra Bioavailable) Tablets

Analytical Development

  • Analytical method development (HPLC, UPLC, GC, IC, Dissolution, NMR, Mass, GC/MS, LC/MS etc)
  • Analytical method validation and transfers
  • Specification setting
  • Stability and Stress testing (Heat, Moisture, Photo, Acid, Alkali, Oxidative etc)
  • Evaluation and method development for various Nitrosamines impurities, Genotoxic impurities in API, Drug product, excipients
  • Preparation of CMC part of a dossier

Biopharmacy

  • Evaluation of similarity between clinical batches
  • Expanded biorelevant dissolution testing and in-vivo co-relation
  • Precipitation inhibitor screening and evaluation
  • Dissolution: USP 1 and 2, Biodiss (USP 3), Macroflux (dissolution-absorption), surface dissolution imaging, flow-through dissolution (USP 4), intrinsic dissolution rate

Clinical Development

  • In vitro in vivo relationship
  • Clinical and preclinical development plan
  • Pilot and pivotal study design (PK, BES, PD, efficacy/safety)
  • CRO qualification, selection by tender process and monitoring
  • Study results evaluation and troubleshooting
  • Medical writing
  • Scientific advice

Regulatory and Pharmacovigilance

From early-stage development through the approval and launch of new product, regulatory experts can assist with all regulatory needs across the entire product lifecycle

Pre-approval

  • Regulatory dossier compilation all modules
  • Regulatory due diligence and strategy incl., scientific advice meetings
  • Product information preparation SPC, PIL and labelling
  • Cooperation with EU agencies for pre-submission activities
  • Support for local specific requirements
  • eCTD publication services

Submission

  • Dossier dispatch, submission of applications, deficiencies management, translation of product information text
  • DTP services i.e. mock-ups preparation and updates
  • RIM data services

Post-approval

  • Portfolio management
  • MA maintenance: variations(Type IA, Type IB, Type II), renewal, and MA transfer, ‘sunset clause’ exemptions package, withdrawal
  • RMS transfers, Industrial transfers support, MAs harmonization strategy proposal and execution, MA duplication procedure
  • Certificate of Pharmaceutical Product (CPP)

Governance

Development Quality Assurance

  • Qualification of equipment and facility for GMP/clinical batch manufacturing
  • Assessment of cleaning validation, cross-contamination, MACO value calculation
  • Product Specification file/ IMPD dossier for clinical batches
  • Release of clinical batches
  • External audit (API manufacturers, CMO)

Project Management

  • Coordination of new project evaluations (timeline, costs, risks)
  • Project definition – detailed planning of timeline, costs, risk and various strategies (formulation, clinical, RA, procurement, IP, etc.)
  • Accountable as development workpackage leader – from project start to Development Dossier Ready
  • Leading the team in subsequent phases that support the overall program – dossier submission, registration, transfer, launch, post-launch support, B2B support
  • Reporting of project updates to management

Contact

Zentiva Group, a.s.
U Kabelovny 529/16
102 00, Prague 10,
Czech Republic

Zent2U@zentiva.com
+420 267 243 231
Copyright Zentiva Group, a.s. © 2024 All rights reserved|created by swallow

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