Sterile preparation

Sterile Products

Type of dosage form of sterile products:

1. Ophthalmic
2. Injectable
3. Powder for injection (Vial)

Gowning System:

In the manufacture of sterile drugs Gowning System is most important.

1) The gown must be sterilized and made of material which will not shed particles.

2) Everyone entering a clean or a sterile area must change gear garments and wear special garments which includes head, musk and footwear.

3) The number of people must be as low as possible and restricted to authorized people.

Environment Monitoring:

Environmental monitoring is one of the most important tasks in the sterile department. It is a regular check of view to take timely corrective measures for maintaining a favorable manufacturing environment, minimizing the risk of product contamination. It is also a part of validation exercise.

The environmental monitoring approach is also adopted to ensure that there is no significant risk of air borne cross-contamination.

Zonal Classification of Clean Room

Airborne particle limit  

 Aseptic Room Preparation:

The purpose of the aseptic technique is to prevent microorganisms from the environment.

To design of an aseptic room the following factors must be borne in mind:

1. Site

2. Size

3. Windows

4. Doors

5. Surfacing materials

6. Services

7. Corridors

The aseptic procedure comprises the following steps:

1) Sterilization of equipments

2) Sterilization of containers

3) Sterilization of gown.

4) Filling of the solution in the containers under aseptic conditions

5) Double door air lock system.

6) Pass box for materials.

Filling containers under aseptic conditions is the most critical step in the production cycle. This technique is filtration sterilization. HEPA (High Efficiency Particulate Air) filter is used. The most effective ones are claimed to retain 99.997% of the particles. Laminar Air flow cabinet is used under HEPA filter. Filling area is class-A zone whereas the background is class-B zone. The processing rooms must be supplied and flushed with air under controlled positive pressure.

Sterilization:

Sterile products can be classified in two classes:

1. Products which can be sterilized in their final container.
2. Products which must be processed under aseptic conditions since they cannot withstand the common methods of sterilization.

Most sterile preparations are aqueous solutions and the method of choice for sterilization is autoclave.

There are 5 types of sterilization:

CONTAINERS:

Containers for injectable preparations are made as far possible from the materials that-

>Are sufficiently transparent to permit visual inspections of the contents, except for implants.

>Do not adversely affect the quality of the preparations under the ordinary conditions of handling, shipment, storage, sale and use.

>Do not permit diffusion or across the walls of the container or yield foreign substances into the preparations. Injectable preparations may be supplied in glass ampules, vials or bottles or in other containers such as plastic bottles or bags etc.

The multiple dose containers may be used for intramuscular, subcutaneous or intracutaneous administration, but no multiple dose containers may contain a total volume of injection sufficient to permit the withdrawal of more than ten doses, unless otherwise stated in the individual monograph. The period of time between the withdrawal of the first and final dose should not be unduly prolonged.

CLOSURES

Vials or bottles with fitted with suitable closures a good seal, prevent the access of microorganisms and other contaminants and usually permit the withdrawal of a part of the whole of the contents of the container without removal of closures. The plastic of rubber materials of which the closure must be compatible with the preparation and be sufficiently firm and elastic to allow the passage of a needle with minimal shedding of particles and to ensure that the puncture is released when the needle is withdrawn.

  

AMPOULE:

Ampoules are the walled glass containers which after filling, are sealed by fusion of the glass. The contents are withdrawn of the glass. The contents are withdrawn after rupture of the glass for one time use.

VIALS:

Vials are thick glass container for dry powders injectable product in which suitable solvents are added to make solution or suspensions just before injections.

WATER FOR INJECTION:

The water which is used as solvent in parenteral product manufacturing is known as water for injections. This water should be highly purified and free from microorganism.

Process Flow Chart:

(Sterile product manufacturing)

Process Flow Chart:

(Vial manufacturing)

Process Flow Chart:

(Ampoule manufacturing)

INFUSION:

According to the FDA Large volume parenterals means a terminally sterilized drug product packaged in a single dose container with a capacity of 100 mi or more and intended to be administered or used as man. It includes IV infusion, irrigating solution, peritoneal dialysis and blood collecting with anticoagulant. These solutions are usually administered by intravenous infusion to replenish body fluid or electrolytes or to provide nutrition. They are usually administered in volumes of 100 ml or1 L or more per day by slow IV infusion with or without a controlled rate infusion system.

Drug International intravenous fluid manufacturing plant may be regarded as one of the most technologically advanced plants in Bangladesh. In designing the whole process, special care has been taken by providing absolute sterile manufacturing condition. The prime feature of the process is that there is no human physical contact with the product at any given time. This has been ensured by way of a series of fully automated manufacturing procedure including robotics. The bottle pack aseptic system (Form-fill-seal or FFS) is a unique and innovative manufacturing technology. Plastic bottles are blow moulded, filled with the solution and seal under sterile condition, in a single working cycle where there is no environmental exposure or human contact during manufacturing. The IV fluids are presented in a scientifically designed bottle where there is an extra protective eurohead cap and a resealable rubber disk. The whole process is performed in a class 100 clean room. The air inside this room is cleaned up to 100 particles per cubic feet passing through HEPA (High Efficiency Particulate Air) filter. This ensures the highest standard of quality and purity in order to ensure the highest level of safety.

References:

1. The Theory and practice of Industrial Pharmacy, 

    (Leon. Lachman, H.A. Lieberman, J.L. Kanig)

2. Encyclopedia of Pharmaceutical Technology

    (James Swarbrick - Taylor and Francis)