Technical - National Center for Therapeutics Manufacturing

Operator-Technician Training

The NCTM’s technical training covers both theory and application of current Good Manufacturing Practices (cGMP) within the pharmaceutical industry, giving new hires a running start and greatly reducing the need for on-the-job training. Our multidisciplinary curriculum offers an in-depth study of upstream and downstream manufacturing processes, sterile environment protocol, bioprocess equipment operations, quality unit operations, documentation practices, and standard operating procedures most common in the pharmaceutical industry.

Introduction to Pharmaceutical Manufacturing

This asynchronous online course comprehensively discusses the fundamental elements associated with the development and manufacture of pharmaceutical products. Training modules discuss the categories of pharmaceutical products, phases of pharmaceutical discovery, development, approval, and varying manufacturing processes (chemical or biological). The curriculum also reviews regulatory agencies and their roles, current Good Manufacturing Practices (cGMP) and GXP, quality assurance and control, and finishes with an exploration of career paths within the pharmaceutical manufacturing industry. 0.2 CEUs

Module 1: Pharmaceutical manufacturing basics, categories of drugs (small/large molecule), target site, drug substance/drug product, industry sectors, types of manufacturing companies (small, large, CMO)
Module 2: Introduction to regulations, major legislation, FDA jurisdiction, FDA enforcement, Standards and Guidelines
Module 3: Stages of the pharmaceutical development process, discovery through IND application, phase I through marketing application, FDA review through surveillance, other licensing applications
Module 4: Manufacturing process, materials and supplies, materials management, drug production process, upstream processes (large vs. small molecule), downstream processes (large vs. small molecule), equipment, master production record
Module 5: Current Good Manufacturing Practices (cGMP), quality system requirements, cGMP compliance overview (quality assurance and quality control), basic cleanroom requirements, dressing for cleanrooms, careers in pharmaceutical manufacturing, job skills overview

Understanding the Science of the Biopharmaceutical Industry

This asynchronous online course provides a pragmatic study in the scientific principles of microbiology, immunology, and basic biochemistry that create the foundation for developing and manufacturing biopharmaceutical products. Curriculum covers biological macromolecules, an intensive study of infectious and non-infectious diseases, the immune system’s structure and function, pathogenesis, and categories, uses, and development process of biotherapeutics and vaccines. 0.4 CEUs

Module 1: Biopharmaceuticals defined, history, manufacturing process, FDA mandates, structure of biological molecules, carbohydrates, proteins, nucleic acids, lipids, and their roles in biologics, infectious diseases, pathogenic organisms, viruses, bacteria, fungi and related diseases, non-infectious diseases, genetic factors vs. environmental factors
Module 2: Immune system, innate vs. adaptive, NK cells, antigen presentation, antibodies, active vs. passive immunity, primary vs. secondary immune response, pathogenesis and routes of entry
Module 3: Recombinant DNA technology, protein therapeutics and gene therapy, targeting activity, monoclonal antibodies, vaccine types, whole vs. partial organism, DNA, effectiveness, duration of immune memory, cost of development, biosimilars

CGMP Procedures and Documentation

This asynchronous online course explains the expectations of and reasoning behind proper documentation protocols mandated in current Good Manufacturing Practice (cGMP) environments, like pharmaceutical production facilities. Topics include principles of data and information entry, technical writing, recording guidelines, document control, and process documentation, including laboratory notebooks, logbooks, standard operating procedures (SOPs), and batch production records (BPRs). Participants will understand the entire documentation pathway from R&D to commercialization of product, including corporate, R&D, manufacturing and qualification/validation. 0.4 CEUs

Module 1: Introduction to regulations in the pharmaceutical industry, Food and Drug Administration, history and legislation, current Good Manufacturing Practices (cGMP), cGMP requirements, Title 21 CFR, federal documents, FDA enforcement, correspondence for nonconformance, importance of documentation, GMP records, “documentation pyramid”, regulatory pathway of drug development, stages, measurable claims
Module 2: Document control, legal requirements for record maintenance, features of controlled documents, system integrity, change control, recording guidelines for entering data/making corrections/signing data/reporting deviations/Corrective and Preventative Actions, reporting to FDA, identifiers and samples, internal auditing, risk levels, employee documentation and training
Module 3: R&D documents/development protocol/records/reports/procedures, log books, Standard Operating Procedures (SOP), SOP development/types/writing/flowchart use/forms, batch records, qualification documentation/activities, validation documentation/plan
Module 4: Fundamentals of technical writing, recording original data, data collection, making entries in lab notebook, recording laboratory procedures/inventions/ideas, attachments, referencing and blank space

Pharmaceutical Facility Operations

This asynchronous online course provides an overview of pharmaceutical manufacturing facilities, including design/layout, utilities, and equipment. Participants will study clean room design, classification, and structure, and understand the many processes that are implemented to ensure a sterile environment, including practicing aseptic technique, gowning, environmental monitoring, and sanitization. Management of chemical and biological waste, sterilization techniques, and equipment maintenance and calibration are also discussed alongside the importance of validation in a pharmaceutical facility. 0.3 CEUs

Module 1: Facility Design Overview (types of facilities, facility design/construction/complexities, utilities design, equipment, startup procedures, and maintenance)
Module 2: Clean Area Design (contaminants, clean room design, clean room classifications, and controlling contamination)
Module 3: Clean Area Operations (aseptic techniques, human and workplace contaminants, clean room supplies and storage, and environmental monitoring)
Module 4: Sanitization and Sterilization (cleaning and disinfection, types of sanitization, reasons to sterilize, Sterility Assurance Levels, and sterilization responsibilities)

Safety in the Biopharmaceutical Industry

This asynchronous online course covers a wide range of safety, health and environmental (SHE) issues specifically related to the pharmaceutical industry, including environmental safety, process and product safety, biosafety levels, industrial hygiene, and physical and chemical properties. Participants will receive an overview of product development stages and vaccine production, and will learn about toxicity, toxicology, drug safety and evaluation, pharmacokinetics and toxicokinetics, as well as risk assessment and analysis. Case studies, historically significant accidents, and lessons learned are incorporated throughout to provide real-life relevancy. 0.3 CEUs

Module 1: Introduction to workplace safety, safety responsibilities, risks and hazards, exposure and routes, toxicity (local and systemic) and effects, types of hazards, case studies, hazardous waste and proper handling
Module 2: Industrial Hygiene, government regulations for the pharmaceutical industry, OSHA standards 29 CFR 1910 (subpart D-J / K-Z), controlling hazards, evaluation, risk assessment, industrial hygiene controls
Module 3: Risk Assessment, processes, Hazardous Operations Evaluations (HAZOP), risk analysis, risk evaluation, risk management
Module 4: Basics of Laboratory Safety, biosafety defined, biosafety levels, CDC lesson, standard microbiological practices, safe storage of toxic materials, lab security, BSLs 1-3, clean benches, biosafety scenarios, case studies

Quality Unit Operations

This week-long, instructor-led course offers a comprehensive review of quality assurance systems and practices, quality control activities, and quality control assays that are relevant to biomanufacturing. Participants learn about best documentation practices, environmental monitoring and microbial testing, as well as the types of products made in biotherapeutics manufacturing and how they are tested. Hands-on lab activities cover aspects of environmental monitoring such as gowning, surface monitoring, viable and total air particle sampling and total organic carbon sampling for water, as well as assays and analytical techniques that are used in the testing of biologics and other therapeutics, including bacterial endotoxin testing, SDS-PAGE assay, total protein assay, and high performance liquid chromatography. 4.0 CEUs

Day 1: Introduction to the Quality Unit, biological laboratory skills safety overview, common lab equipment, pH and conductivity, balances and pipetting, light microscope, aseptic technique on the bench, aseptic technique in the biological safety cabinet
Day 2: Cleanroom gowning and de-gowning, air monitoring: total and viable air particle monitoring overview and practice, surface monitoring: overview and practice, environmental monitoring, air and surface monitoring sample collection/preparation, total air particle
Day 3: Bacterial Endotoxin Testing (BET), gel clot assay, results and calculations, final product assays, Total Organic Carbon (TOC) analysis (SST), Total Organic Carbon (TOC) analysis (Unknowns), High Performance Liquid Chromatography (HPLC)
Day 4: Overview and practice of Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), Total Organic Carbon (TOC) Results, methods of biomolecule analysis, HPLC results review
Day 5: Overview of total protein assays, Bicinchoninic Acid (BCA) assay for total proteins, Surface monitoring results, air monitoring results, SDS-PAGE and BCA results, Quality Assurance review

Upstream Manufacturing of Biologics

This week-long, instructor-led course provides a comprehensive overview of the techniques and challenges involved in the upstream processes for manufacturing biologics. Lectures and laboratories cover types of biologic products, an overview of upstream processes, producing biomass using various platforms, an overview of cell lines, an overview of bioreactors and their operation, and the analytics used to evaluate upstream production. Applied hands‐on training includes preparation and proper labeling of reagents and media; aseptic technique; plasmid extraction, purification, and quantitation; restriction enzyme digestion and agarose gel electrophoresis; cell banking, counting and passaging; bioreactor assembly, sterilization, and operation; microbial cultivation and inoculation of seed culture; fed‐batch and batch fermentation, and harvest and storage of biomass. Reusable versus single‐use systems are discussed. 4.0 CEUs

Day 1: Introduction to upstream manufacturing processes, bacterial transformation of E. coli, BioFlo 310 Fermentor overview/assembly/controller
Day 2: Culture media preparation, mock BPR and calculation, steam sterilization, filter sterilization, fermentation overview, seed culture and cell banking overview, cultivation of seed culture, determination of transformation efficiency
Day 3: Inoculation of BioFlo 310 Fermentor, batch and fed-batch fermentation, offline analysis: practice on OD, pH, and Brix analysis, sample collection and analysis, plasmid purification: isolation of plasmid, sample collection and analysis, quantitation of purified plasmid, additional analysis
Day 4: Harvest and storage of biomass, offline analysis: summary of fermentation run, overview of cell culturing, counting and passaging of mammalian cells
Day 5: Purified plasmid analysis overview, restriction enzyme digestion, agarose gel electrophoresis, In silico analysis and discussion

Downstream Manufacturing of Biologics

This week-long, instructor-led course provides a thorough review of the most commonly utilized techniques involved in the downstream processes for manufacturing biologics. Lectures and labs cover concepts in sterile buffer preparation, initial product clarification and recovery, various modes of filtration and column chromatography. Applied hands-on training include techniques in buffer preparation, sterile filtration, cell lysis, centrifugation, product clarification, tangential flow filtration, UNICORN chromatography software training, column packing, ion exchange and hydrophobic interaction chromatography. Select activities are instructor-led, so participants can be exposed to operating pilot-scale equipment after learning techniques and concepts at small scale. Critical parameters to be considered during each unit operation along with available single-use options are also discussed in this course. 4.0 CEUs

Day 1: Overview of downstream equipment, introduction to buffers and molarity, buffer prep calculations, buffer preparation activity and sampling, aseptic assembly and sterile filtration, large-scale buffer with BPR, filter integrity testing
Day 2: Microfiltration and Tangential Flow Filtration (TFF) overview, microfiltration activity, cleaning, storage and NWP calculations, TFF concentration, TFF diafiltration, analysis of samples, mass balance calculations
Day 3: Introduction to cell lysis, cell cake solubilization, clarification activity: tubular bowl centrifuge demo and turbidity measurements, cell lysis activity: homogenization of cells, primary recovery and clarification, centrifugation of feed material, large-scale depth filtration demo and turbidity measurements
Day 4: Introduction to column packing and qualification, AKTA Pilot chromatography system and column packing, column packing calculations, Unicorn Software overview and practice, evaluation of column packing, column sanitization and cleaning
Day 5: Introduction to Ion Exchange (IEX) Chromatography, feed material preparation, method preparation, IEX chromatography method and analysis of results, Introduction to Hydrophobic Interaction Chromatography (HIC), HIC method and practice