Drug Product R&D

Avista Pharma Solutions has a best-in-class, full service pharmaceutics group that can support formulation development and early to late phase Drug Product manufacturing. We have extensive experience in selecting the appropriate formulation technology based on physiochemical properties, drug metabolism and pharmacokinetic data.

 

Avista Pharma has a core strength in improving oral bioavailability of poorly soluble compounds through solubility and/or rate of diffusion using particle size reduction, cyclodextrins, pH adjustments, solvents, emulsions, microemulsions, spray dried dispersions and combinations of these technologies. Our experience includes preformulation, GLP toxicology studies and First-in-Human (FIH) formulation selection and manufacturing for over 21 compounds that have progressed into human clinical trials. We have successfully formulated compounds with particular challenges such as food effects, pH solubility dependence (e.g. proton pump inhibitors in humans) and poor solubility. The best-in-class pharmaceutics groups is also experienced in pharmacy compounding and pediatric formulation development. Our current GMP capabilities allow us to Support Phase I/II manufacturing & packaging of clinical supplies and pilot-scale support of technology transfer for tablets, capsules and parenteral formulations to Qualified Commercial Manufacturers for later stage products.

Preformulation Capabilities Include:

  • API physiochemical evaluation
  • Solid state chemistry – salt selection, polymorph screening, amorphous dispersions, crystallization development
  • Excipient compatibility

Formulation Development Capabilities Include:

  • Discovery and GLP formulation optimization
  • Multiple formulation platforms for small molecules:
    • API milling – cone milling, ball milling and jet milling
    • Powder in Capsule and Powder in Bottle (micronized as needed)
    • Experience developing immediate release tablets & capsules
    • Controlled release tablets
    • Enabled formulations for low solubility compounds: amorphous spray dried dispersion, hot melt, lipidic/microemulsion
    • Lyophilized and solution parenteral development
    • Pediatric formulation development and manufacturing
    • High-Potency Compounds

First In Human Drug Product Capabilities Include:

  • Tablet development lab: high shear granulator, roller compactor, tablet press, fluid bed dryer, and spray dryer
    • Small scale equipment allows for efficient utilization of API
    • Equipment train matches typical scale-up for GMP manufacturing

Packaging and Labeling Capabilities Include:

  • cGMP drug product manufacturing suite and bottling/labeling line
    • cGMP Class 10,000 Manufacturing Suite/Class 100,000 Packaging Suite
    • Xcelodose for rapid powder in capsule filling
  • Late stage development
    • Strong track record of technology transfer of manufacturing processes to cGMP manufacturers
    • Quality by Design (QbD) process evaluation using FMEA model
    • Determination of Critical Process Parameters (CPP) and Critical Quality Attributes (CQA)
    • Statistical Design of Experiments (DOE)

Stability Studies

Pharmaceutical stability testing is conducted to determine how the quality of API, drug substance or drug product varies with time under the influence of environmental factors such as temperature, humidity and light. These studies also help determine optimal storage conditions, product quality and expiration date(s). Avista Pharma has over 3,000 square feet of Stability areas that include over 25 chambers for pharmaceutical stability studies across three (3) locations. We can accommodate studies of various container and lot sizes, temperatures, humidities, lights and lengths of study. With fully-compliant GMP analytical chemistry and microbiological labs, Avista Pharma is your one-stop Stability Testing Partner with redundant storage locations for business continuity. The ICH Guideline Q1A is the consensus document for performing stability studies, and depending on your product, region and study goal.

 

In this Guideline, the following conditions are recommended:

 

  • 25°C ± 2°C / 60%RH ± 5%RH
  • 30°C ± 2°C / 65%RH ± 5%RH
  • 40°C ± 2°C / 75%RH ± 5%RH
  • 5°C ± 3°C
  • -20°C ± 5°C
  • -70°C ± 15°C

 

Avista Pharma has validated chambers for each of these conditions, and is capable of validating additional chambers to conditions specific to your custom study as well. All chambers are electronically monitored 24 hours / 7 days a week and have backup power in case of a power interruption. In addition to the traditional shelf-life stability studies, Avista Pharma routinely performs specialized studies to help determine performance characteristics of your product.

 

These studies typically involve:

 

  • Freeze/thaw or other temperature cycles
  • IV set/drug compatibility studies
  • API/container compatibility studies
  • Dose solution stability
  • Photostability studies

 

Photostability studies are performed to ensure that no significant loss of drug product or drug substance occurs with exposure to light. Our chamber exposes the samples to conditions within ICH Guideline Q1B:

 

  • not less than 1.2 million lux hours
  • not less than 200 watt hours