Since the pandemic, a truly reliable supply chain has become like gold dust. This has created huge demand for sourcing agents who do all the leg work. One such company, Syntec Pharma, has received a stern warning letter from the FDA as to the multiple bad practices at their facility in the US.
When inspectors looked at the facility near the end of 2020, they identified a whole host of issues that needed to be addressed to ensure safety of the final products. After some back and forth with the agency, Syntec volunteered some solutions in hopes of rectifying its concerns. However, as of the end of July 2021, these measures were found to be insufficient and a warning letter was issued.
These bad practices included a few primary issues revolving around the organisation of the company's drug manufacturing facility and its lack of conformity with cGMPs.
Mix-ups
One aspect that the inspectors found to be a problem was that Syntec did not perform repackaging, relabelling, or holding of API under the appropriate cGMPs. This is normally done to avoid mix-ups and loss of API purity.
This concern was exemplified when, after stating that it did not repackage any HPAPI, it was found that Syntec did in fact charge a customer for prepackaging a cytotoxic chemotherapy agent. Subsequently, Syntec explained that it "occasionally perform[s] repackaging, but could not remember the specific Lomustine repackaging activity". The FDA stated that this "lacked basic documentation of the operation, including a batch record and equipment use log".
The FDA did acknowledge the company's attempt to implement good documentation practices
Another example of this was the number of inappropriate storage conditions that were found at the facility. This included chemicals stored at room temperature that should have been refrigerated, APIs stored alongside weed killer, and personal food items stored with unidentified products in unlabelled aluminium bags in the refrigerator where API and chemicals were also stored.
Syntec's proposed solution to this was to "divide the pharmaceutical storage area into four sections by using a separate shelf for each of the following categories: cytotoxic compounds, beta-lactam, other potent compounds, and other API". This was by no means enough in the FDA's eyes as the agency explained that this failed to identify the risks associated with these drugs.
Cleaning
Another aspect of record-keeping that was found to be lacking was the written and validated procedures for cleaning equipment. Use of equipment for highly potent APIs was not documented as well as whether cleaning was performed.
Not only were appropriate logs and validation not performed, but inappropriate cleaning agents were also used. Such as laundry detergent for ventilation hoods, which was not validated.
When responding to the FDA, Syntec used the phrase "visually clean" when talking about how tools were assessed before use, saying that this means the risk of contamination was "exceedingly small". Unsurprisingly, the FDA replied that this "did not provide compelling evidence to support that cross-contamination has not occurred for your APIs that have been distributed".
Current GMPs
There is a pretty long list of ways in which the facility did not meet cGMP standards, which meant that the company lacked adequate quality unit oversight for the manufacture of APIs.
The FDA did acknowledge the company's attempt to implement good documentation practices, however, the agency did not deem its efforts enough as they were still lacking in many big picture instructions. These included things like a corrective action and preventive action (CAPA), supplier qualification programmes, and master production instructions for future API manufacturing operations.
On top of this, there were also concerns about the source of some of the company's drug products. A few of the API suppliers Syntec engaged were sending product that was subject to an import alert at the time. These were for various reasons, but one was from a facility that was "delaying, denying, or limiting FDA inspections".
This amounts to receipt of adulterated drugs and is a violation that needs to be addressed.
Back and forths
Despite a few back and forths between the agency and the company that attempted to rectify the situation, the FDA found that Syntec's responses to the issues were inadequate to rectify the situation. On this basis, the FDA "strongly recommended" Syntec Pharma engage a GMP consultant to thoroughly evaluate its entire operation.