A Facilitator’s Guide to Enrich Current Good Manufacturing Practices (cGMP) for Radiopharmaceutical Production in Academic Facilities.
Capstone – Career Goals
- Develop a GMP training program for use in academic institutions that manufacture radiopharmaceuticals.
- Showcase this training program as an accomplishment during a new role.
- Assume the role as a Pharmaceutical Quality Assurance Director.
- Either join or create a regulatory consulting firm that specializes in auditing GMP based facilities.
Objective
The objective of my capstone is to develop a Facilitator’s Guide that focuses on improving current Good Manufacturing Practices (cGMP) training. The goal is to provide a simple and cost effective way for academic facilities to improve their cGMP training techniques. Inadequate and/or ineffective GMP training can lead to FDA issued 483s (notices following FDA inspections, indicating inaccuracies and insufficient records of a FDA-regulated study) as well as warning letters, manufacturing downtime, increased maintenance costs, product quality issues, and frequent employee turnover. The Facilitator’s Guide will focus on teaching employees the relevant cGMPs, as well as target some areas of interest uncovered during this project. These areas of interest will be informed by literature reviews and completed surveys from professionals in academic radiopharmaceutical facilities, to promote optimal methods of cGMP training.
An outline of the cGMP content that provides context for the Facilitator’s Guide:
- Principles
- Personnel
- Facilities
- Equipment
- Manufacturing
- Labelling
- Manufacturing and Distribution Records
- Quality Assurance and Quality Control
In order to enhance existing cGMP training topics, the Facilitators’ Guide will cover a number of crucial topics disclosed by literature reviews as well as surveys from GMP professionals. If sufficient information can be found from the literature and from the survey responses and interviews, the following topics of interest may be added to the Facilitator’s Guide:
- Results of the survey (see attached Survey of GMP Professionals)
- Benefits of group facilitated training, applying case studies
- Problem solving activities and role playing activities during training
- Methods to improve work specific area training
- Applying better on-the-job training methods
- The importance of continuing education in cGMP
- Understanding that “SOP Training ” is only part of what employees need to know
For this capstone, the facts and materials underlying these cGMP issues will be obtained through the course of interviews and surveys with professionals involved in cGMP manufacturing, as well as reviews of publications. The Facilitator’s Guide will be targeted to academic facilities that are looking for new avenues of cGMP training, or frequently do not have sufficient funding to hire third party trainers to teach employees cGMPs, or have dealt with cGMP violations in the past, and for facilities that are strictly using “SOP-based Training” techniques. My current proposal aims to develop a robust cGMP Facilitator’s Guide that enhances basic training requirements to address topics of special interest in product manufacturing.
Background
Current Good Manufacturing Practices (cGMP) are regulations established by the US FDA under the Federal Food, Drug, and Cosmetic Act [1]. During the early years of the 20th century, the federal government did not have many regulations protecting communities from dangerous food and drug products. Following notable drug and biologic product failures and product incidents, the federal government (FDA), in due course, created cGMPs which are regulations that ensure the quality of medical products including drugs, biologics, blood products and medical devices [2]. Also, the regulations helped ensure the safety, identity, purity, efficacy, potency, stability, and consistency of individual batches of regulated drug products through manufacturing and testing in accordance with pre-defined processes, methods, and specifications [2].
Currently, facilities that manufacture food and drugs for human consumption must follow regulations regarding design, monitoring, control, and maintenance of manufacturing processes and facilities [3]. Some of these regulations include, [21 CFR Part 210—Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drug], [ 21 CFR Part 211—Current Good Manufacturing Practice for Finished Pharmaceuticals] and [21 CFR Part 11—Electronic Records; Electronic Signatures]. These guidance’s help ensures the safety of the drug before it reaches the consumers. [3]
During the manufacture of any drug product it is important to properly train staff on guidance’s that govern manufacturing, data integrity and quality. The lack of training can lead to improper techniques and non-compliance. Manufacturing facilities that are inspected by the FDA may be subject to 483s (letters indicating inadequacies or insufficiencies), warning letters and even “cease and desist” orders. 483’s are confidential and not publicly available, but there are statistics on GMP- based warning letters issued over the past few years. Between 2007-2014, the FDA issued a total of 997 warning letters that were cGMP based violations. About 685 (68.7%) warning letters were issued to medical device companies, 223 (22.4%) to facilities manufacturing pharmaceuticals, (5.7%) to active pharmaceutical ingredients (5.7%), (1.8%) for biological products and (1.4%) for pharmacy compounding. [4] During inspections the main areas of focus for the FDA are to examine a company’s quality system and evaluate any areas flawed in manufacturing, reviewing customer complaints, recalls, deviations, quality control and quality assurance, and manufacturing failures [4]. During these audits, it is important to demonstrate that GMP facility management has provided sufficient resources to develop and implement an adequate training program to all employees’ job related functions as well as all aspects of FDA compliance. Developing a cGMP Facilitator’s Guide for radiopharmaceuticals would help promote improved manufacturing practices and create a suitable environment for compliance.
Methodology
During this research project, a number of sources of data will be used to develop the Facilitator’s Guide. The primary methods for this research project will include both literature reviews and surveys with researchers and individuals who work in the GMP environment to assess factors that enhance or limit GMP training.
- Basic content of GMP will be reviewed by thorough examination of the Code of Federal Regulations (CFR), along with literature searches.
- For the Facilitator’s Guide: Considering the percentage of warning letters issued between 2007-2014, this research project will include a literature search for recurrent categories of insufficient manufacturing practices identified by the FDA. If recurrent categories of deficiencies are discovered, these categories will be addressed in the Facilitator’s Guide, to bolster the educational process with the aim of teaching GMP facilities’ employees about specific pitfalls to avoid.
- For the Facilitator’s Guide: During the GMP professional’s interviews, I plan on using a survey (see attached Survey of GMP Professionals for content) to obtain information, such as how GMP facilities train new employees on relevant cGMPs, if their employees are familiar with the guidance’s that govern manufacturing and quality, and if they find their training programs (if applicable) to be cost-effective. Interviews with researchers from the University of Pennsylvania, University of Southern California, the University of Washington, Washington University at St. Louis, Memorial Sloan Kettering and the University of Alabama Birmingham. Interviews will be recorded, and the Survey of GMP Professionals completed and results analyzed.
Combining the data from the literature reviews and the results of surveys will provide the basis for developing the GMP Facilitator’s Guide. The project will comprise a research paper summarizing the background and rationale for the project, the results of the literature review as well as the surveys and interviews, and the complete Facilitator’s Guide.
