Manufacturing APIs for Injectables Requires a Safety-First Approach

Maintaining Clean Room Operations is Key to Safety, 5 Best Practices to Follow

Posted: February 9, 2021

API Manufacturing and Pharmaceutical Manufacturing

These days there has been lots of talk about injectables – especially when it comes to COVID-19 vaccines. But aside from vaccines, drug are produced in injectable form to treat a variety of conditions. The benefits of injectable drugs are that they provide rapid delivery of a drug or vaccine , and can often be targeted to a specific location, such as the cornea to treat eye disease (ophthalmic). Unlike drugs delivered in pill form, injectables don’t have to travel through the body before they reach their ultimate destination – it’s more of a straight shot. Yet, injectables aren’t always needed, or helpful for many chronic conditions when pills are more convenient and just as effective. Yet, when they are needed, injection of drugs can be delivered as intradermal  (between the layers of the skin), as subcutaneous  injection (in the fat layer) and intramuscular (in the muscle) injections.  

Regardless of the way injectable drugs are delivered, the fact that they directly enter the bloodstream makes their safety and sterility of critical importance. The dangers of not heeding extreme care for sterility was all too evident in 2017 quite tragically at the New England Compounding Center. Tainted steroid injections caused hundreds of people across the country to become infected with meningitis.

Because of their potential to cause harm or death if not manufactured properly, the Active Pharmaceutical Ingredients (APIs) that are delivered via injection in finished drug products must follow rigorous quality controls standards to ensure the sterility of the drug and the elimination of residual toxins. For this reason, only the most qualified and experienced Contract Development & Manufacturing Organizations (CDMOs) should be considered to produce them.

Below are five best practices and Standard Operating Procedures (SOPs) that we at Seqens CDMO NA follow when it comes to manufacturing injectables:

  1. Manufacture in world-class cleanrooms. Good Manufacturing Practice (GMP) suites, which are cleanrooms, are designed to ensure that very low levels of  dust, airborne organisms or vaporized particles are in the air. The cleanliness is rated by the number of particles per cubic meter at a predetermined molecule measure. Seqens’ suites have been validated to class 100,000.
  2. Test and repeat. Each injectable API goes through rigorous testing.  After we produce an API we send a sample out to a microbiology lab for endotoxin studies, where it’s grown to determine the level of bacteria present – such as salmonella, fungi or other residual bacteria. Since we make APIs often in specific solvents, many are good at killing live organisms, yet some actives that come out of water can have higher levels. The tests are conducted by heating the samples in a petri dish to see if anything grows (since in organic chemistry those types of microbes cannot survive in organic media, they need water and oxygen and warm conditions).
  3. Attire the staff. Each employee entering our GMP suites is gowned from head to toe, wearing masks at all times.  Each person washes and dries exposed body parts, such as face and hands, before putting on gloves and garments. In addition, all staff working in or near the GMP suite or handling the materials in any way are required to have a flu shot and be free of any illness.
  4. Follow rigorous equipment protocols. This is established by assessing the toxicity and potency of the existing residues on potential human consumers of the next product to be manufactured by the same equipment. Cleaning procedures are based on the nature of the residues, the equipment design and the expected effectiveness of the procedure. These procedures can employ rinsing, soaking, or spraying equipment surfaces with a liquid medium. It can also include boiling a solvent inside the enclosed space of a piece of equipment, and manual scrubbing or wiping equipment surfaces.
  5. Use the most advanced air filters. When manufacturing APIs for injectables the rule is that we conduct sterile manufacturing, followed by sterile filtration, followed by gamma radiation. We use specialized sterile filters which trap and capture any bad actors.

Manufacturing for injectables can be a specialized expertise and we’re fortunate to have the skill-set and GMP facilities here in Newburyport to support it. Our capacity, however, is for smaller batches, yet being part of a global CDMO, enables us to provide our sponsors with the ability to scale up production for very large quantities from our sister plant in Finland, which specializes in them.

TECH TRANSFER

Critical drug ingredients that directly enter a patient’s bloodstream can be a lifesaver, yet proper precautions must be taken with injectables to ensure their safety though effective clean room procedures and sterile conditions. It’s an exact science that leaves no room for errors. 

For more insights, check out: Whose Manufacturing Your Prized API?, How to Stem the Flow of Tainted Generic Drugs, or Coming Clean on Cleanroom Operations in GMP Manufacturing. Please consider singing up for our newsletter here.