For Contract Manufacturing Organizations (CMOs) operating in compliance with current Good Manufacturing Practices (cGMP) there are two necessities. The first is an unassailable quality management system. The second, related to the first and equally important, is having qualified personnel who can competently perform all the functions necessary to develop APIs for clinical trials and commercial manufacturing.
It doesn’t matter how many graduate degrees staffers have or whether they earned their Ph.D.’s at Ivy League schools or state schools. In the complicated business of drug development, it’s not good enough to be a top-notch chemist. Of course it’s important. So are good problem-solving skills. But in the heavily regulated pharmaceutical industry, it’s also critically important for all those working in drug development to stay up to date and thoroughly understand the demands and expectations of the regulatory agencies.
The regulations are numerous. They also change. Keeping up with those changes is a constant challenge for all involved, from the people in the stock room who store the raw materials that arrive at the plant to those at the other end of building who perform the manufacturing and everyone in between.
As we discussed in our article, How to Select a CMO: 7 Steps of a Productive Quality Assurance Audit, a good CMO remains alert by reading FDA warning letters and enforcement actions. These can identify trends and insights that are useful if you want to avoid running afoul of the FDA’s hot button issues du jour, which could cause project delays. That monitoring alerted us to the FDA’s recent scrutiny of data integrity. Since our own focus at Seqens is to keep projects on time and on budget, it’s important for us know these things so we’re prepared.
Keeping up to date and being aware of what the FDA is gunning for is still not enough. We must maintain each staffer’s level of qualification for their job in order to assure project integrity. That requires us to have a robust training program in which every employee participates.
At Seqens, our quality assurance training program begins with all new employees going through an extensive series of training activities before they are even allowed to do anything in the lab or plant, never mind perform any of the responsibilities for which they were hired.
3 training categories
Our training falls into three broad categories:
- First among these is our cGMP Orientation Training Program, which is mandatory prior to performing any work independently. An annual refresher is also required.
- Following close behind is training related to Environmental, Health and Safety procedures.
- Then, ongoing job-specific skills training is implemented for each employee.
QA is in charge of training
To determine what training each person needs, the Quality Assurance (QA) department maintains a comprehensive training matrix for every job description and job function (see sample, Fig. 1).
Job-specific training requirements are determined by department managers. QA then manages the training program in accordance with the comprehensive matrix and also by providing the GMP Training, updating training files, and assisting in the design and development of training materials or courses.
Some common topics for training include:
- USP compendial requirements – standard USP requirements that related to all drug products.
- ICH guidelines.
- Relationship between ICH guidelines and the Common Technical Document.
5 types of training activities
Training activities can be categorized in five types:
- Knowledge based self-study.
- One-on-one individual training.
- Instructor-led training.
- On the Job training.
- External training.
One goal of our training is to assure that when people study the various Standard Operating Procedures (SOPs), they also learn the many nuances involved, as for example how fast or slow to perform a procedure.
While 85 percent of our training is done in-house, we on occasion send people out for training on such topics as maintaining equipment, new analytical technique or new chemistry technologies, and of course we all attend industry-specific meetings to learn about the latest developments.
Quality Control – getting their instrument rating
Airplane pilots don’t fly planes until they have their instrument rating and can demonstrate they know what every switch and control does, why, and how to operate it. Lives depend on it. At Seqens we also have many instruments used in Quality Control (QC) for all the small molecule chemistry we are developing and that will eventually become a pharmaceutical product.
Lives depend on us too. The APIs we develop have to be free of impurities. That’s why we have to make sure any staff members who uses instruments to test compounds has full command of the equipment. Depending on their job function, there are 12, 16 or 18 modules our QC people must complete within their first six months with us.
GMP orientation training program
Everyone, including the CEO, participates in our GMP Orientation Training Program annually. The multipart training includes a GMP refresher and any protocol changes or tweaks required by regulatory bodies.
Then, depending on job specific-roles, GMP training is tailored to the individual. For example, all the R&D folks in our Devens, MA facility come to our manufacturing facility in Newburyport when their product runs in the GMP suites. However, we cannot allow anyone to do any work in the cGMP suites until they are fully GMP trained. That training takes a number of hours and covers a whole host of SOPs. We make sure only staffers who are proficient can touch equipment or perform any procedures or testing.
Training varies in intensity and scope, depending on job function. For example, it is less rigorous in the kilo lab than in the cGMP lab.
Fig. 1. Ongoing training is mandatory for all Seqens personnel
How long does training take?
General orientation takes a couple of days, while QC training can take months to complete all the specific modules assigned by the QA department and department managers.
Working at a CMO involves not just quality training but operational training as well. These are simultaneous endeavors. A new hire goes into the lab, gets oriented on how the lab works and at the same time starts on the training modules. He or she must be proficient before actually going ahead and testing any chemistry.
The GMP lab is an auditable environment – mistakes cost dearly
Why so much focus on training? There are many reasons, chief among them is that if someone makes a mistake, we have to open an investigation. That takes a lot of work. So it is really important to limit mistakes with training and more training. The GMP lab is an auditable environment and the devil is in the details.
You have to know, for example, how to property document things. You can’t use pencil. It has to be written in black or blue ink, and if you cross anything out you have to initial it. And so on.
Health, safety and environmental procedures training
Another CMO training focus is health, safety and environmental training.
We handle chemicals, many of which are hazardous. Consequently we must abide by OSHA’s mandatory Process Safety Management training rules. Anyone who comes in contact with hazardous materials has to be well versed in the following:
- Proper way to label hazardous materials or waste.
- Handling of the specific hazardous materials used.
- Proper protective equipment.
- General rules and regulations on safeguarding workplace health, safety and the environment.
Generally speaking, handling larger amounts of hazardous material triggers a greater amount of training than handling small amounts. How much contact someone has with these materials and how often is also a factor in how much training is needed.
Training records FDA inspectors look for
CMOs are subject to FDA inspections. Good FDA inspectors come through the door and ask for these three things right off the bat:
- Customer complaints.
- Preventive maintenance records – documented evidence that we are maintaining our equipment.
- Training records for everyone who touches GMP products.
A Ph.D. makes you a chemistry expert. High quality training fills in what you need to know to create high quality APIs.
Training is very important, and we spend a lot of time and resources to keep our staff up-to-speed on the latest regulatory issues as well as the latest trends in API manufacturing. We share that knowledge with our sponsors to make sure we’re on the same page. And most of what we write for the blog is designed to be educational. Check out blogs such as “Qualifying vs Validating Analytical Methods in GMP Manufacturing: How to Choose the Best Approach” or “Transferring API Technology to a CMO? Use This Checklist” – that are designed to serve as a resource to people inside the company as well as sponsors. To learn more, contact us at email@example.com. We will respond quickly!