YalePharma Services

YalePharma offers a wide spectrum of services and expertise in scientific, professional, technical, manufacturing, quality control, and regulatory fields in compliance with applicable cGMP/GLP regulations. Services include formulation development, drug delivery design, analytical method development/ validation, drug stability assessment, clinical and commercial scale manufacturing, labeling, packaging, and shipping. The company also possesses state-of-the-art supercritical fluid (SCF) units for small-scale isolation, extraction, and purification of drug moieties. Finally, YalePharma provides documentation and regulatory support for DMF preparations and IND, NDA, and ANDA submissions.

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

1. Development of In Vitro Efficacy Models (e.g. inflammation, oncology)
2. ADMET to Support Lead Optimization (e.g., cytotoxicity, protein binding, CYP induction/inhibition, Caco-2)

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

GLP Toxicology & Pharmacology

1. Pharmacokinetic and toxicokinetic studies
2. Pharmacodynamics
3. General Pharmacology Study (in vitro and in vivo)
4. 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

 

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

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
YalePharma developed proprietary, patented platforms for specific clients and partners, including the following:

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

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

Clinical & Commercial Manufacturing and Re-packaging

Solid Oral Dosage Forms: The firm 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
The firm 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