I. Biodefence

Biodefense and Emerging Pathogens Screening System

Robotic Drug Screening System

II. Research Models and Services

Research Models

* Rats
* Mice
* Guinea Pigs
* Hamsters
* Gerbils
* Rabbits
* Rhesus Monkeys
* Cynomolgus Monkeys
* Immunodeficient Models
* Disease Models
* Transgenic Models

Research Animal Diagnostic Services

* Microbiological Services
* Laboratory Animal Pathology Services
* Clinical Pathology
* Plasma Biomarker Analysis
* Serology Services
* Serology Reagents
* Infectious Disease PCR Testing
* In Vivo Biosafety Testing

Surgical Services

* Vascular Catheters
* Non-Vascular Catheters
* Soft Tissue Procedures
* Neurological Procedures
* Cardiovascular Procedures
* Device Implants
* Telemetry Devices

Avian Products and Services

* SPF Eggs and Chickens
* Avian Services
* Chicken Cell Products
* Mycoplasma Reagents
* Antigens and Antisera
* Custom Virus Preperations

Antibody Production Services

* Antigen
* Polyclonal Antibodies
* Monoclonal Antibodies

Research Animal Facility Equipment

* 8' Semi-Rigid Isolator
* 3' Semi-Rigid Isolator
* 6' Flexible Isolator
* Isolator Glove Sleeve Clamps
* Transfer/Shipping Isolator
* Gnotobiotics Transfer Chamber
* Adjustable Shipping Chute
* U.V. Shipping Container Disinfection System
* Stationary Disinfectant Immersion Station
* Narrow Disinfectant Immersion Cart with Splash Containment

III. Biopharmaceutical Services

Product Programs

* Cell Therapy
* Gene Therapy
* Monoclonal Antibodies
* Recombinant Proteins
* Viral Vaccines
* Xenotransplantation
* Human & Animal Derived Products

Process Programs

* Cell Banking & Characterization
* Cell Storage & Stability Testing
* Virus & TSE Validations
* Protein Characterization
* Release Testing
* Product Stability Testing
* Archiving

Testing Programs

* Adventitious Agents & Retroviruses
* Analytical Chemistry & Custom Assay Validation
* Cell Characterization
* Human & Specific Viruses

* Molecular Testing & DNA Detection

IV. Preclinical Services

Discovery Services

* Medicinal chemistry for evaluating, validating and optimizing active compounds for a discovery program
* Hit to lead chemistry
* Lead optimization chemistry
* Custom focused libraries synthesis
* Synthesis to establish structure activity relationship (SAR)
* Chemistry and synthesis route development
* Synthesis of reference compounds, scaffolds, building block and starting materials

Discovery Lead Optimization

* Custom Medicinal Chemistry
* In vitro ADMET Tiered Evaluation Assays
* Cytotoxicity
* Solubility
* Permeability
* Metabolic Stability and Rate
* Protein Binding
* CYP450 Inhibition
* CYP450 Induction
* Interspecies Comparison
* Metabolite Identification
* In vivo validation of ADMET
* PK/Bioavailability
* Animal Models
* Pre-IND Toxicology Studies

In Vitro Drug Screening

• * Development of In Vitro Efficacy Models
  * ADMET to Support Lead Optimization

  * Cytotoxicity
  * Solubility
  * Permeability
  * Metabolic Stability and Rate
  * Protein Binding
  * CYP450 Inhibition
  * CYP450 Induction
  * Interspecies Comparison
  * Metabolite Identification

GLP Toxicology & Pharmacology

* Pharmacokinetic and toxicokinetic studies
* Pharmacodynamics
* General Pharmacology Study (in vitro and in vivo)
* Toxicology studies

* Single dose toxicity (acute toxicity)
* Subacute to chronic toxicity
* Subchronic
* Chronic
* Genotoxicity

－Ames
－Chromosomal Aberration
－Micronucleus

* Reproductive Toxicity

－General Reproductive Toxicity (Segment I)
－Teratogenicity (Segment II)
－Per and post-natal Toxicity (Segment III)

* Carcinogenicity
* Local Tolerance
* Special Toxicity studies

－Immunotoxicity
－Studies as requested or designed

Pathology Services

* Bone and Joint Pathology
* Medical Device Pathology
* Histomorphometry
* Immunohistopathology
* Neuropathology
* Reproductive Pathology
* Toxicologic Pathology
* Molecular Pathology
* Ultrastructural Pathology
* Transgenic Phenotyping Pathology
* Archiving

Testing of Active Pharmaceutical Ingredients (API’s) and Excipients

• Comprehensive testing consists of chromatographic, spectral, thermogravimetric, differential scanning calorimetric, and LC/MS techniques.

Pre-formulation Studies

To develop dosage forms to achieve enhanced solubility, sustained delivery, enhanced stability, targeted delivery, improved bioavailability, acceptability for specialized use, and administration for alternate routes, systematic pre-formulation studies are conducted at YalePharma facilities. Listed below are some of the critical tests that YalePharma scientists can perform:

* Solubility profile
* Partition coefficient
* pH rate profile
* Bulk density
* Polymorphism
* Particle size distribution
* Flow properties
* Stability
* Dissolution
* Drug-excipient interaction
* Log pKa
* TGA/DSC

Development of Dosage Forms

* Oral dosage forms (conventional and extended release) - Tablets, Capsules, Liquids
* Parenterals - Liquid and Lyophilized
* Semi-solids - Gels, Ointments, Creams
* Rectal/Vaginal - Suppositories, Solutions, Ointments

Drug Delivery Systems

* Microencapsulation Controlled release
* Sublingual
* Transdermal Gels

Analytical Methods

* LC/MS
* High performance liquid chromatography (HPLC)
* Gas chromatography
* UV/Visible spectrophotometry
* Log pKa/Log P Determination
* Supercritical Fluid Separations

Analytical Method Development

* Raw material testing
* Packaging material testing
* Stability indicating assay
* Dissolution testing
* Cleaning residues - swab and rinse samples
* Residual organic volatiles

Analytical Method Validation

* Recovery
* Accuracy
* Precision
* Repeatability
* System suitability
* Specificity- forced degradation studies
* Solution stability
* Ruggedness
* Robustness

YalePharma Data Management

* Adapting of protocols to capture unexpected observations
* Calculating of QC across historical results
* Combining data, charts, analysis and images into study reports
* Searching across studies

Stability Assessment

* Stability protocols follow current practices incorporating ICH guidelines, which are
implemented to determine the stability of the finished product in the proposed container-closure system. YalePharma’s facility is equipped to conduct stability studies under the following storage conditions, but can meet other, more specialized conditions upon customer request.

Stability Conditions:

* Long-term: 25° ± 2°C, 60% ± 5% RH for 3, 6, 9, 12, 18, 24, and 36 months
* Intermediate: 30° ± 2°C, 60% ± 5% RH / 65% ± 5% RH for 1, 2, 3, and 6 months
* Accelerated: 40° ± 2°C, 75% ± 5% RH for 1, 2, 3, and 6 months
* Accelerated: 50° ± 2°C, 75% ± 5% RH for 1, 2, 3 months
* A reference sample will be stored under ambient conditions unless specified otherwise
* Freeze-thaw (-20°C to ambient)
* Photostability

V. Clinical Services

Phase I Services

Laboratory & Analytical Sciences

* Central Laboratory Services
* Bioanalysis
* Pharmacokinetics
* Clinical Pathology

• Independent Review Board (IRB)/Ethical Review

  Quality Assurance
  

• VI. Endotoxin and Rapid Microbiological Products

• Contract Testing

  Endosafe Research Products

  • * YPENDO

FDA Licensed LAL Reagents and Instrumentation

* Kinetic LAL Reagents
* Gel-clot and End-point Reagents
* Accessory Products
* Kinetic LAL Plate Readers
* Robotic Instrumentation
* Endotoxin Detection Software

Rapid Microbiological Methods

* YPENDO
* YPOR
* YPRE

• VII. Reproductive Endocrinology Services

• Animal Research Models

  • * Androgenic Activity
    * Anti-Androgenic Activity
    * Antifertility Activity
    * Anti-Glucocorticoid Activity
    * Anti-Myotropic Activity
    * Anti-Ovulatory Activity
    * Anti-progestational Activity
    * Estrous Cycle Suppression
    * Fertility Suppression
    * Glucocorticoid Activity
    * In Vaginal pH/Irritation Assay
    * Myotropic Activity
    * Ovulatory Activity
    * Progestational Activity
    * Spermicidal Intravaginal Administration
    * Steroid Testing
    * Testicular Morphological Assessments

  Female Fertility

  • * Hormone Testing
    * Endometriosis
    * Amenorrhea
    * Uterine fibroids
    * Ovulatory disorders
    * Recurrent miscarriage
    * Tubal disease
    * Menopause

Male Fertility

* Semen analysis
* Sperm preparation for intrauterine insemination
* Full service andrology testing
* REI Laboratory

VIII Other Cervices

Manufacturing Process Development and Validation

* Liquid orals
* Tablets
* Capsules
* Semi-solids (gels, lotions, creams)
* Solid dosage forms (suppositories)
* Parenteral (both liquid and lyophilized)

Solid Oral Dosage Forms:

* YalePharma has all necessary equipment for manufacturing solid oral dosage forms, including tablets and capsules of various sizes. Additionally, YalePharma has the necessary infrastructure and experience for the storage, distribution, and documentation for clinical supplies intended for all phases of NDA. Dedicated employees monitor all activities for clinical supplies and commercial batches.

* For other dosage forms, including parenterals and semi-solids, the firm has capabilities to manufacture pilot batches. For production batches, outside sources with demonstrated compliance profiles and cost effective budgets are selected. YalePharma coordinates scale-up and technology transfer activities to maintain continuity as well as to provide overall assurance for meeting delivery schedules.

Documentation and Regulatory Submission Support

* YalePharma has extensive experience in DMF and CMC preparation, for providing regulatory support for IND, NDA, and ANDA submissions.

Consultation

* Product/process development
* Facility design, development, and validation
* Evaluation of pharmaceutical systems and equipment
* Scale-up and technology transfer