Primary packaging suppliers are reporting investments in order to increase the use of primary materials pre-sterilized, “Ready to Use” (RU). These materials open up new possibilities and opportunities in the design of sterile manufacturing areas.
2. What’s a Ready to Use Material?
“Ready to Use” (RU) materials are primary packaging materials which are sterilized by the supplier.
The sterilization process is usually performed by a different company that the packaging material manufacturer.
The current sterilization systems could be:
- Ethylene Oxide (ETO) or pure steam for glass material.
- Irradiation for plastic material or elastomeric.
The material, once sterilized, came back to the primary material manufacturer which is responsible for the analysis and testing, in order to release the material as validated sterile material; another possibility could be to send the material directly from a sterilization company to the final user, in this case final user is responsible for testing and sterile release.
3. Primary material
Materials and forms suitable to be sterilized as Ready to Use materials are:
Prefilled Syringes (PFS)
In the field of PFS, RU materials have a wide range of use; in fact RU materials are the current standard for pharmaceutical manufacturers
- Syringe with or without needle: In the case of syringes without needle (Luer-Lock or Luer-cone forms) PFS are supplied with cover (Tip Tap). In the case of syringes with needle PFS are supplied with protection (Needle shield).
- Syringes can be supplied in glass (sterilized by the supplier by means of ETO) or in copolymer plastics, COP o COC (sterilized by irradiation).
- Syringes are packaged in the form of “nest” with 100 to 160 pieces per nest.
- Stoppers: Sterilized by irradiation or pure steam.
On the field of vials RU materials are less used, mainly due to the price. But taking into account the current investments of primary material suppliers, a significant price drop is expected in the next coming years.
In the field of vials RU materials are:
- Vials: Sterilized by means of ETO or pure steam.
- Stoppers: Sterilized by means irradiation or pure steam.
- Capsules: Sterilized by means pure steam.
RU vials are packaged on the form of “nest” or in trays, ready to be loaded in the filling machine.
In the field of cartridges RU materials are:
- Cartridges: Cover is included. Sterilized by means ETO or pure steam.
- Stoppers: Sterilized by means irradiation or pure steam.
Cartridges are packaging on the form of nest, ready to be loaded in the filling machine.
RU primary materials, along with the use of filling lines “COMBO” type have a wide series of advantages, which could open new opportunities to small and medium size pharmaceutical manufacturers.
- Avoiding washing machines, autoclaves, depirogenization ovens, along with associated process.
- Avoiding all utilities required by these equipment.
- Only one filling machine is capable to manage the filling process for several pharmaceuticals forms: PFS, Vials, Cartridges )
- Only one sterile area is required for processing several pharmaceuticals forms ( PFS, Vials , Cartridges)
Less Operation Costs:
- Fewer specialized personnel: At least one person in the washing and sterilization area.
- Less energy cost: Less equipment and fewer filling areas.
- Less quality and maintenance cost for the equipment.
- Less cost due to changeover.
- Less cost due to sterile areas and clean room qualifications.
- Less cost due to “cosmetics “ deficiencies in the primary material ( RU packaging avoid the contact glass-to-glass)
– RU primary material price: RU prices, both vials and cartridges, are still high, but a constant price drop is expected during the next 2-3 years, as result RU materials prices will match the ratios for PFS in the range of 1 bulk to 2-3 RU.
– More dependence on the primary materials suppliers : It could mean longer delivery times and minimum order requirement. That makes logistics more complex and requires a good planning to match supplies and production.
6. Sterile areas design
Once the decision about RU materials is made, it is necessary to study carefully the implication on the sterile area design:
– The savings in space and utilities due to the absence of some complex equipment (washing machines, ovens, tunnels, smaller autoclave…)
– Debagging flow for RU primary materials.
– Waste flow due to the debagging operations.
– Decision about the best solution for the filling room in the sterile area: (Filling area 100% laminar flow, RABS or laminar flows just under the filling machine surrounding by B class areas or Isolator).
– It is very important taking into account the design of the area after filling process: inspection, labelling, plug rod insert for PFS, safety elements, collection of final products on trays, secondary packaging…) in order to make the process as much efficient as possible
7. Possibility of COMBI lines
Pharmaceuticals manufactures in the process of decision to start with sterile manufacturing projects, should take into account on its decision matrix the option of systems based on RU materials and COMBI lines for sterile filling. Due to the important implications of this kind of decision, on the point of view of facilities, investment and costs, it is highly desirable a thorough economic study, by means of a simulation process, taking into account all the variables involved on the process: Savings in investments, savings in operation cost, increase of material cost, pharmaceutical forms and expected yearly forecast. Once the decision is made about to launch this kind of project it is very important to keep the unity of the concept in the project, avoiding splitting the project in disconnected tasks, with different people in charge, internal and external, which could cause discrepancies, inconsistencies and misunderstandings. The project should be managed as a compact whole, by integrating every part under an only one management: Design, Engineering, Materials and equipment selection, Installation, Commissioning, Qualifications and Associated Quality System. This last item is very important; Quality System must be implemented from the very beginning and it has to follow the project through every step and finally linked it, in a compact and continuous way, to the industrial production stage.