A Guide to Aseptic Filling in Pharmaceutical Engineering Projects – From Methods to Machinery

The term ‘septic’ comes from the Greek word ‘septikos’, meaning “characterized by putrefaction”, which refers to decomposition of flesh after death. However, today the word ‘Aseptic’ conveys freedom from any rot, filth, bacteria or viruses that could cause disease or death. The practices and procedures of aseptic techniques involve applying stringent protocols to minimise the risk of infections.  Aseptic manufacturing, processing and filling play vital roles in the pharmaceutical industry.  Ensuring a stringent environment during manufacturing is critical, and maintaining identical conditions through the filling stage is equally essential.

As specialists in aseptic filling, we offer you insights into comprehensive aseptic filling solutions in pharmaceutical engineering projects.

FILLING METHODS

The importance of precision in filling holds immense significance. During the filling process, avoiding under-filling and over-filling is crucial to avoid wastage. Filling methods include piston pumps, diaphragm pumps, or peristaltic pumps.

Piston Pumps – This is the most common method to fill liquid products. Piston pumps maintain aseptic integrity because of their high filling accuracy and precision, particularly for low fill volumes (≤0.3 mL). These pumps are known for being most effective for filling sterile, water-thin products such as parenteral drugs and shear-sensitive liquids

Diaphragm Pumps – Offering a highly accurate volume control, the diaphragm pumps are used for transferring fluids from one place to another and for ultrafiltration or diafiltration purposes.

Peristaltic Pumps – The peristaltic pump covers diverse filling volumes from 0.1ml to 500ml, varying with different hose diameters. This pump encloses the fluid or product within pharmaceutical-grade tubing, the sole component in direct contact with the fluid. Thus, peristaltic pumps are suitable for single-use aseptic filling, eliminating cross-contamination between batches.

However, these methods follow the sterilisation of drug containers viz. vials, syringes, cartridges, ampoules, and bottles. The sterilisation process is lengthy and aims to achieve a completely aseptic environment.

CONTAINER PRE-STERILIZATION METHODS

Dry Heat Sterilization – This method is most commonly used in glass containers due to their sensitivity to moisture and steam. Dry heat is used to sterilise or depyrogenate the containers for a specific duration to ensure sterility. Temperatures usually range between 176 and 232 degrees Celsius. The period is usually around 60 minutes or based on the characteristics of the item being sterilized.

Autoclaving – Autoclaves are steam sterilisers. In this method, the containers are placed in an autoclave that uses high-pressure steam to kill harmful bacteria, viruses, fungi, and spores on items that are placed inside a pressure vessel. The moisture in the steam efficiently transmits heat, destroying the microbial structure.

Radiation Sterilization – This is a non-thermal sterilisation involving gamma irradiation, electron beam irradiation, beta particles, or ultraviolet light.  It is used to damage the DNA of microbes and render them ineffective. Radiation is an excellent alternative for products intolerant to heat or chemicals.

Chemical Sterilization – Chemical Sterilization involves the use of chemical agents such as hydrogen peroxide, chlorine etc to kill unwanted microorganisms.  This method is best suited for materials intolerant to heat, high pressure, irradiation, or filtration.

Filtration – Filtration involves drug products going through sterilization filters. The filters then trap and remove microbes, maintaining the product’s sterility and safety. 

The most common containers used for aseptic filling are glass, metal, and plastic, such as PET.

TYPES OF FILLING LINES

1. Liquid Filling Line – Operating on high pressure, this method involves liquid flow into bottles using its own weight. The process occurs when the pressure of the liquid reservoir matches the amount of air present in the bottle. The fillers offer easy control and precise filling, adapting to different-sized bottles without part replacements. The machine also has the added feature of halting the process in the absence of a bottle on the belt.

• Vial filling Line – Compact and cost-effective fillers, vial filling machines are equipped with sensors to ensure uniformity by identifying and rejecting improperly filled vials. These machines maintain accuracy through weight checker mechanisms, ensuring consistency in weight for reliable and standard productivity and quality control.

• Powder filling Line – Powder filling machines are semi-automatic or fully automatic with a reliable rate of output. They work at high speed with an average of 108 strokes per minute, making them one of the most preferred options in various industries.

• Ampoule Filling Line – This process covers the product entirely in the inert glass with no direct exposure to rubber stoppers or other elements. Ampoule fillers are designed specifically to fill ampoules. Their filling capacity ranges from 1ml to 20ml, catering to a variety of ampoule sizes and providing flexibility in the filling procedure.

• Pre-filled Syringe Line – This syringe and closing machine processes disposable and nested syringes. This system allows gentle transfer of the pen tub to the filling machine. Size changeovers are easy to execute, and settings for dosing volume, filling needle movement and stopper position are easily reproducible.

Fabtech has played an instrumental role in advancing aseptic filling expertise in pharmaceutical engineering projects. Our portfolio includes innovative and tailored fill and finish solutions, aseptic containment technologies, spanning vial filling and capping machines, FilPac prefilled syringe machines, isolators and more. All our machines conform to good manufacturing practices guidelines for pharmaceuticals, meeting the most stringent quality requirements of the pharmaceutical industry. Our machinery has earned a significant presence in numerous prestigious pharma and biopharma projects across many nations. Because of the right mix of promise and performance, Fabtech continues to garner increasing recognition among medical professionals.

Our commitment to healthcare is evident through solutions that drive successful turnkey pharmaceutical engineering projects, enhancing access to life-saving medicines and contributing to the noble endeavour of building a healthier tomorrow!