St. Francis, Wisconsin USA

GMP intermediates, APIs and excipients

(Kingchem Laboratories, Inc.)

Click each drop-down list below (+) to view the supporting list for each topic, or use the Expand All button above to open all drop-downs on this page at once.

MANUFACTURING CAPABILITIES

Our St. Francis, Wisconsin manufacturing plant has an experienced team that can engage at every phase of drug development, from pre-clinical through commercialization. The facility, Kingchem Laboratories Inc., offers full cGMP production for GMP intermediates, APIs and excipients, and can include the upstream integration of RSMs available through our plant in China. Click on the link below for the plant’s Chemistry Capabilities.

Chemistry Capabilities+

Acid Chloride Formation
Aminations
Anhydrous HCl Handling
Azeotropic Distillation
Cycloadditions
Cryogenic Crystallization
Cryogenic Reactions
Elemental Bromine Handling
Esterification/Hydrolysis
Friedel-Crafts Chemistries, Vinyl and Aromatic
Grignard Chemistries
Heterocycles
Hydride Reductions
Lewis acid catalysis
Lithiation Chemistries
Oxidation Chemistries
Reformatsky Chemistries
Reduction Chemistries
Solid Form Manipulation
Steam Distillation
Transfer Hydrogenation
Transition metal catalyzed coupling reactions

CORE TECHNOLOGIES

To see a list of the plant’s core technologies use the drop down box below. To view the chemical structures of our St. Francis Wisconsin plant’s core technologies, click here.

Core Technologies+

Friedel-Crafts Reactions
Grignard Reactions
Reductions
Oxidations
Chiral Chemistries
Carbocycles (Representative Compounds)
Heterocycle Chemistry (Representative Compounds)

QUALITY ASSURANCE

The facility’s manufacturing and quality systems strictly adhere to ICH Q7 standards for Active Pharmaceutical Ingredients. ICH quality guidelines are incorporated into all aspects of our business. An effective Quality Management System led by our Quality Assurance group helps to achieve products that are consistently manufactured and controlled. KLI is registered under the U.S. FDA’s Drug Establishment Registration and is subject to routine inspections by the FDA.

Quality Systems - Compliance+

Supplier Quality / External Audits
Internal Self Inspection Audits / Quality Improvement Initiatives
Agency / Client Audits
FDA cGMP, WI Division of Food Safety
Investigation Review
- Root Cause Analysis
- Corrective Action Preventive Action
Quality Metrics
- Data Compilation / Trending

R&D CAPABILITIES

The issues facing the industry around regulations and guidances such as Quality by Design and Q11 require that a fundamental understanding of the impact of impurities on the API quality is of utmost importance. Our analytical scientists, work hand-in-hand with process chemists, and have the tools and expertise to understand the issues related to fate-and-purge of impurities, as well as high level structural elucidation.

Laboratories in Wisconsin+

R&D Laboratories
- 5 Research hoods
- 2 Walk-in hoods (to 35-L)
- 1 Distillation hood
- 5-L Hydrogenator
- Rotary Evaporators (1 to 20-L)
- Fractional Distillation to <1 torr
- Chromatographic purification
- Explorer Microwave system

R&D Analytical Instrumentation+

GC: 5
HPLC: 8
GC-MS: 1
LC-MS: 1
NMR: 3
UV/VIS: 1

Scale Up: Process+

Internal Kickoff Meeting
- Review Project Scope
- Assign Team
- Activity Review and Timeline Assignment
- Identify Action Items
Raw Materials
- Qualify as Needed
- Order
External Kickoff with Customer
- Team Teleconference
- Scope and Timeline Discussion
- Identify New Information
- Establish Communication Schedule

From R&D to Production+

Development of Process in R&D
- Informational Review
- Laboratory Familiarization Experiments
- Preliminary Risk Analysis
- DoE for QbD
  - Design
  - Lab Record (~Protocol)
  - Execution
  - Iterative Analyses
- Report
Transfer to Manufacturing
- Best Process Description (BPD)
Best Process Description from R&D
- Master Batch Record Compilation by Process Support
- R&D First Review, Preliminary HazOp
- MBR Adjustment to Equipment
- QA, QC, Operations Review
- Final Approval
Process Hazard Analysis
- EHS Personnel Compile Draft
- R&D Chemist for CIM, Special Potential Hazards
- Nodal Analysis
  - What If
  - Risk Analysis
- Departmental Reviews
Operator Training

Kingchem St. Francis Wisconsin Plant

Production Bay 2

Distillation

1500-gal Hastelloy C22 Reactor with Sparging Capability

AFD

316L Stainless Steel AFD with Glove Box

AFD Glove box

KEY FEATURES

Production assets at Kingchem Laboratories range from pilot plant to full commercial scale and include a variety of materials of construction including glass-lined, stainless steel, and Hastelloy. Click on the below links for our plant’s key features and site certifications.

Facility Features+

cGMP: FDA registered for GMP manufacturing of pharmaceuticals (APIs, pharmaceutical intermediates, excipients).
Experienced Staff: Key staff with 10-30 years in GMP manufacturing from CDMO to large pharma.
Facility Footprint: 33,000 sq. ft.
Reactor Volume Range: 35-6,300 L
Reactor Temperature Range: -78°C to 160°C
Reactor MOC: Stainless Steel, Glass-lined, Hastelloy
Pressure: Up to 6 bar (90 psi)
Distillation Capabilities: 20 L – 800 L, 20°C to 250°C (hot oil), <1 mmHg, 5-10 theoretical plates

Production Site Certificates+

FDA Drug Establishment Registration
State of WI, Dept. Safety and Prof. Services – Pharmaceutical Manufacture
Food Processing Plant (Facility Identifier: 12671692120)
FSSC 22000 Certification
Kosher Certification (Chicago Rabbinical Council)
Halal Facility Certification (Islamic Services of America)
CTPAT certified

COMMERCIAL PRODUCTION

With each project, we set an accurate, timely schedule for our customers. Starting from either technology transfer or route selection through process R&D and scale-up, our customers enjoy our proactive and responsive style of communication and collaborative work ethic. In this way, we ensure consistent and robust production to meet your clinical and commercial needs.

Distillation Units - Production Bay 1+

Structured packing
Up to 25 theoretical plates
2x 5-gal Glass-lined
- Electric heating mantle (up to 200 °C)
- Vacuum <1mmHg
30-gal Stainless Steel
- Fractional (up to 160 °C)
- Vacuum <1mmHg
200-gal Glass-lined
- Hot oil (up to 250 °c)
- Vacuum <1mmHg

Distillation Units - Production Bay 2+

Structured packing
Up to 20 theoretical plates
50-gal gal Glass-lined
- Hot oil (up to 250 °C)
- Vacuum <1 mmHg
50-gal Stainless Steel
- Fractional (up to 160 °C)
- Vacuum <1 mmHg
200-gal Stainless Steel
- Fractional (up to 160 °C)
- Vacuum <1 mmHg

Reactors – Production Bay 1+

Temperature range: 0-160 °c
50-gal Glass-lined
50-gal Stainless Steel
200-gal Glass-lined
200-gal Stainless Steel

Reactors – Production Bay 2+

Temperatures as low as -78 C with certain vessels
Pressure up to 90 psi
500 gal Glass-lined
500 gal Stainless Steel
200 gal Glass-lined
1500 gal Hastelloy

Solids Handling - Portable Filters+

- 18-inch diameter monoplate SS pressure filter {holds approx. 30 kg
- 80-gal jacketed pressure SS nutsch {holds approx. 75 Kg)

Solids Handling - Agitated Filter Dryers+

0.6 m2 Stainless Steel
- Holds approx. 100 kg
1.5 m2 Hastelloy
- Holds approx. 400 kg
2.5 m2 Stainless Steel
- Holds approx. 600 kg
Side Discharge
Adjustable Discharge Rate
Bulk Packaging
Custom sized Packaging
- Mimic ILC Dover continuous liner system
- Filled units are placed inside a second appropriately sized outer LDPE bag
- Double bagged units are then placed inside a secondary container of the appropriate size and material of construction
- In some cases, multiple smaller units can be placed inside a large drum
Packaging Room for sub-dividing bulk lots
Class 8 (meets class 100,000 clean room)

Cryogenic Capability+

500 gal Stainless Steel Vessel
Reaction Temperatures to -75 ⁰C
Jacket Temperatures to -90 ⁰C
Closed loop thermal fluid using Syltherm XLT
Liquid Nitrogen cooled with Heat Exchanger

API MATERIAL HANDLING

API Material Handling & Packaging Room+

Pharmaceutical-standard cleanability
ISO 8 (Class 100,000) HVAC
Class 1 Division 2 Groups C&D Electrical
Customer viewing areas
Single-direction flow airlocks
Separate gowning, de-gowning
Controlled equipment/material-handling access
Walk-in hood, spot ventilation arm
Flexible specific-operations PPE donning
Primary focus:
- Final packaging
- Sampling
- Client-configuration divisions
Allowances for future technology additions

Warehousing+

General Storage
Controlled room temperature storage
3x Cold Storage Units
- Temp: 2-8 °c

QUALITY CONTROL

Our research chemists and quality control personnel hold educational credentials from Bachelors through Masters and PhD. The majority of experience ranges from 10-30 years in the pharmaceutical industry. Our team excels at synthesizing advanced intermediates and active ingredients and developing commercial processes to be run at Kingchem’s manufacturing facility in WI.

Kingchem has a strong QC department with dedicated specialists for developing (or transferring in from customer), optimizing, and validating analytical methods. Our instrumentation list is continuously growing and using software such as Chromeleon and Omnic 9 insures that we meet all of the 21 CFR Part 11 requirements for data integrity.

Analytical methods can be transferred in from customer or developed in-house or at one of our other locations such as Dalian or Fuxin.

Analytical Methods+

Transfer and Validation
- Approach per USP and ICH Q2 (R1)
- Protocols and Reports
  - QA approved
  - Client Approval Option
Validation Protocol
- per USP and ICH Q2 (R1)
- Method Dependent
- May include linearity, accuracy, precision, sensitivity, specificity, LOD, LOQ, etc.
- Execution Time ~ 3 Weeks per Method

Support Functions

- Raw material release and qualification
- Routine production analyses (IPC)
- Release testing for production
- Support quality assurance

Analytical Instrumentation (cGMP-Compliant)+

All instrumentation is regularly calibrated by original equipment manufacturers.

Agilent HPLC 1290 Infinity II (cGMP-Compliant)
Agilent GC FID 6890
Agilent GC HS 7697A
Chromeleon (21 CFR Part 11 compliant software FDA Integrity)
Corona VEO CAD
FTIR (Thermo Nicolet IS5)
- (with Omnic Part 11 compliant software)
UV/Vis Spectrophotometer
Millipore Milli-Q Water System
NMR (PicoSpin 80)
NMR (Nanalysis 100Pro)
Melting Point
Refractometer
Metrohm KF Coulometer
Metrohm Autotitrator
DSC

Further Equipment+

Further equipment

Mass Spec (R&D only)
Sampling booth
- HEPA fan filter unit
- Slightly positive pressure to corridor
- Local exhaust for employee safety
- Logbooks
- Rotate cleaning solvents
- IQOQPQ
- Meets class 7 (class 10,000)