The Staff PET Radiochemist is principally responsible for the routine production and quality control of novel and literature radiotracers for clinical and pre-clinical use at BWH cyclotron and associated radiochemistry facilities (BWH-BICOR) within the Division of Nuclear Medicine & Molecular Imaging.
This position acts as an assistant to the Director of Radiochemistry Research & Development in the implementation and optimization of radiochemical syntheses and analytical methods to support candidate novel and literature molecular imaging biomarkers for clinical and preclinical use. Additionally, the Staff PET Radiochemist may develop and compose CMC documentation in collaboration with the Director of Radiochemistry R&D for inclusion in US FDA IND applications.
The incumbent, being recognized as a qualified aseptic PET GMP operator, is also responsible for supporting the routine production of FDA-approved radiopharmaceuticals by the BWH-BICOR in all facets of the operation, when able, inclusive of synthesis, quality control, ISO-classified cleanroom management, and raw material control in accordance with applicable regulatory guidelines and hospital policy. The Staff PET Radiochemist must have above average to superior working knowledge of principles related to chemical syntheses and analytical methodology commonly utilized in radiolabeling and radiopharmaceutical manufacturing processes. Reports to the BICOR Director with dotted line to Director of Radiochemistry R&D
PRINCIPAL DUTIES AND RESPONSIBILITIES:
The major responsibility of this position is to routinely produce the highest quality radiopharmaceuticals and radiotracers for human use on a regular basis with full regulatory compliance. This involves but is not limited to:
Work with BICOR Director of Radiochemical R&D and project Principal Investigators to select potential compounds of interest
Work with BICOR Director of Radiochemical R&D, the BICOR Director, and PIs to develop a budget and schedule to bring a compound of interest into use for pre-clinical and/or human studies
Advise and support efforts by PIs to develop novel compounds, particularly with identifying creative approaches to radiolabeling methods for target compounds
Work with BICOR management and PIs to define, budget, and introduce new equipment for project-specific production and quality control testing needs while meeting all applicable regulatory requirements
Automated Synthesis Modules
In collaboration with the Director of Radiochemical R&D:
Read and understand published literature describing chemistry processes necessary to produce compounds of interest including if needed, the processes to produce starting compounds.
Translate published processes or develop new processes to allow radiolabeling of compounds of interest as needed to allow automated synthesis using any of the BICOR owned synthesis modules.
Adapt, modify, or invent synthesis modules or components to allow efficient production of compounds of interest.
To develop or adapt in process analytics and methods to demonstrate manufacturing process control
To devise product delivery and sampling methods as needed.
To establish methods to clean, calibrate, maintain, test, troubleshoot and maintain modules
Instruct fellow GMP PET operators at BICOR to set up, test, and operate automated synthesis modules
To run synthesis batches when necessary to support research programs and ANDA radiopharmaceutical batch release
In collaboration with the Director of Radiochemical R&D and the BICOR quality unit:
Translate published quality control methods from literature or industry-recognized guidelines to the BICOR quality lab using existing equipment
Assist in the development and optimization of analytical methods
Develop standards and reagent kits for calibration and quality testing of compounds of interest
To develop methods to clean, calibrate, set up, and standardize analytical instruments as a part of BICOR's commitment to continuous quality improvement
Perform quality control tests as needed to support research projects and ANDA radiopharmaceutical batch release
Product Filling in conjunction with PET GMP manufacturing staff
Follow BICOR manufacturing procedures to fill batch final product vials.
Devise means to clean, calibrate, and set up kits, instrumentation, modules, and aseptic processing environments for product filling
Specify required labeling
Perform fraction and filling operations if needed to support research projects
Develop and properly complete appropriate SOPs and batch records for compounds of interest as a PET GMP operator
Develop qualification protocols for compounds of interest in collaboration with the Director of Radiochemical R&D
Conduct qualification and complete analysis of data
Review batch records and supporting data for the purpose of assessing product performance over time
According to the appropriate SOP, submit in writing the circumstances and corrective action for all batches for human use that do not pass quality control criteria (OOS reporting)
Submit this document to the Change Control Committee (CAPA)
Defines adequate levels of chemicals and disposables for new compounds
Sets up receiving, quarantining and qualification of chemistry reagents and materials in accordance with cGMP for new compounds
Good Manufacturing and Good Laboratory Practices
Follow all hygiene and gowning protocols
Maintain clean and orderly workspaces within a PET GMP manufacturing facility and associated cleanrooms
Control all in process and waste materials
Assist BICOR management in maintaining records for all process equipment, environmental control equipment, and quality control instrumentation
Radiation Safety Practices
Operates the radiation monitoring system in accordance with SOP's
Performs all aspects of radiation exposure and release practices
Participates in the investigation and resolution of all anomalous occurrences
In collaboration with the Director of Radiochemical Research & Development:
Prepares chemistry methods and controls (CMC) documentation for literature and novel compounds consistent with requirements for IND, NDA, ANDA, RDRC or other regulatory pathways.
Prepares and executes qualification and stability protocols for literature and novel compounds
Completes data summary and analysis in support of agency submissions
Supports the BICOR quality unit in responding to internal and external inquiries regarding chemical quality control methodology.
Cyclotron Operation (may be trained during employment at BWH)
Determine the type of cyclotron target and liquid/gas preparation for a compound under development
Determine the appropriate cyclotron run parameters to produce radio isotopes
Operate cyclotron as needed for process development
Minimum required qualifications:
One of the following:
BS in Chemistry with a minimum of 6+ years of direct experience in PET IND radiosynthesis meeting the requirements of USP < 823> and/or 21 CFR 212. OR
MS in Chemistry with a minimum of 3+ years of experience in organic synthesis of compounds, radiometal chemistry, analytical chemistry, of other field applicable to chemical synthesis or quality control. OR
MS/PhD in Chemistry with a minimum of 2+ years of direct experience in PET IND radiosynthesis meeting the requirements of USP < 823> and/or 21 CFR 212
Post-graduate experience in radiochemical synthesis is highly preferred.
Experience in quality control methodology for quantification and identity of chemical moieties in analytical samples, including experience with the following modalities:
High Performance Liquid Chromatography
Thin Layer Chromatography
Experience in biologic quality control testing of sterile products, including
Filter Integrity Tests
Chromogenic Endotoxin Tests
Upon departmental orientation and annually thereafter, must complete training which includes:
Other testing at the discretion of the BICOR quality unit
Strong command of the English language.
Functional ability to write clear concise working documents targeted to internal and third-party review.
Exceptional ability to work with sustained attention and care on technically demanding tasks with narrow time constraints.
Exceptional time management and organizational skills, and a keen ability to prioritize multiple tasks to meet the clinical needs of the department.
Ability to perform mathematical calculations.
Ability to conduct oneself in a professional and courteous manner and maintain strong working relationships with Chemists, Physicians, Nurses, Pharmacists, and other allied health care professionals.
Working knowledge of medical terminology, abbreviations and instrument operation pertaining to nuclear medicine and radiation safety
Ability to organize and maintain efficient work areas and services.
Ability to make critical decisions based on knowledge of chemistry, pharmacy, and cGMP requirements.
Ability to distinguish routine functions from those requiring the professional judgment of a pharmacist or other state-licensed practitioner.
Experience with the production of C-11, N-13, and F-18 PET radiopharmaceuticals highly desired
Experience with production using automated synthesis units for F-18 and C-11 radiopharmaceuticals highly desired
Strong competence in PET radiopharmaceutical quality control methodology including High Performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC), Liquid Chromatography/mass spectrometry (LCMS), gas chromatography (GC), and chromogenic endotoxin testing highly desired
Experience with the concepts and requirements of radiochemical purity, radiochemical yield, chemical purity, and specific activity.
Experience with radioactive detectors including dose calibrators, solid state detectors, and sodium iodide well counters.
Experience with cGMP laboratory procedures.
Experience utilizing USP chapters to support work performed within the GMP manufacturing environment.
Fluency with desktop computing and the Microsoft 365 suite
Ability to spend most of the work time standing or walking to complete daily tasks.