Recently, three clients of contract manufacturer Berkshire Sterile Manufacturing (BSM) had a special request for the CMO. Could BSM manufacture three sterile drugs that would serve as treatments for COVID-19? And, instead of the normal three- to six-month turnaround time, could they do it in four weeks?
BSM responded immediately. The staff worked long hours and volunteered overtime on weekends to meet the four-week deadline and make these essential medicines available as quickly as possible.
PDA interviewed BSM CEO Shawn Kinney, PhD, about how the company answered the call.
PDA Letter: Are the drugs aseptically filled or terminally sterilized?
Kinney: All of the COVID-19 drugs that we are working on are sterile filtered and aseptically filled.
PDA Letter: Are any of them biologics? If so, do they require lyophilization?
Kinney: Two of the drugs are biologics but they are not being lyophilized. At this point, BSM does not believe that the clients are interested in long-term stability as much as quick delivery to the clinic to demonstrate efficacy.
PDA Letter: Can you give us an idea of how the filling area is arranged? Are you using isolators or a restricted access barrier system (RABS) or a combination?
Kinney: All of the filling is accomplished in isolators. RABS are used to protect mouseholes leading into and out of the isolators. We have two isolator lines, one manual line and one semi-automated line. A robotic isolator system is in progress but will not be operational until late 2021.
BSM staff fill COVID drug into vials
PDA Letter: How do you ensure stability of these products in such a short period?
Kinney: BSM is not performing stability studies for these clients. If stability is being performed, it is being performed by the client or by a contract lab. The client is so focused on getting as much product to the clinic as possible that stability may be determined later.
PDA Letter: Since BSM is making and filling three different products, what sort of cross- contamination measures are you following, e.g., disposables, separate dedicated lines, etc.?
Kinney: All of the COVID-19 drugs are being produced using disposable technologies for all product contact equipment. They are filled in isolators with new sterile gloves every run. Isolators are cleaned after every run and sanitized to a validated 6-log reduction before every run.
PDA Letter: Is BSM also manufacturing other, non-COVID-19 drugs? If so, how does manufacturing ensure that production of these medicines is not disrupted?
Kinney: At this point in time, BSM has been able to add overtime and weekend work and utilize overflow days to fit in COVID drugs without impacting existing clients.
PDA Letter: What kinds of technologies does BSM use to ensure both high quality and quick release for these very critical drugs?
Kinney: Release testing is performed by traditional QC methods and sterility testing is outsourced. We coordinate with the sterility lab for testing. The lab is very understanding of the importance of COVID-19 drugs and puts the samples on test immediately. We rush the internal testing with overtime if necessary. Quality is always foremost in our mind. QA keeps up with the review of testing results and documents as soon as they are available.
PDA Letter: Is the company using rapid-sterility testing? If not, is the company considering it?
Kinney: BSM is not using rapid-sterility testing at this time. The validation of the rapid test is time-consuming and, right now, we are focused on rapid delivery of as many units as possible. Until the products are demonstrated to be efficacious, there is no reason to consider validating rapid test methods.
PDA Letter: Since these are existing clients, has this changed how Berkshire works with the U.S. FDA and other regulatory agencies in this initiative?
Kinney: BSM has had two successful preapproval inspections in the past two years. Our clients own the drug products and regulatory filings with the FDA. BSM is prepared to provide any support necessary and welcomes any FDA inquiries, inspections or other actions to get rapid approval of these drugs if they are efficacious.
How Do These Products Treat COVID-19?
Drug Product 1
This product disrupts a protein in the inflammation pathway to prevent inflammation in the lungs and prevent patients from needing ventilators. This product was filled March 20 with a scheduled release date of April 10. Another batch of this drug will be filled on April 12.
Drug Product 2
This product is an immune-system booster expected to help a patient fight the virus. It is produced through a two-part fill on April 3 and 8.
Drug Product 3
This product comes in two forms (long-lasting or short-lasting) and increases oxygen uptake in the lungs by improving oxygen permeability in the lungs. The long-lasting form is a liposomal product. Each form was filled on April 4.
Information courtesy of Sarah Kinney, Quality Control Associate (Analytical) at Berkshire Sterile Manufacturing.