Introduction
GEA Pharma Systems Ltd specialise in Buck
Systems™ Contained Materials Handling solutions for Primary and Secondary
Pharmaceuticals and Healthcare. With extensive experience within the Generics
sector, The Buck Systems™ range of technologies and equipment that improve and
enhance the efficiency and performance of Solid Dosage Form Plants.
The experience gained in the Generics sector ensures that all Buck Systems™
equipment and technologies are suitable for the very stringent demands of
production performance, plant and market flexibility (single and multi product)
and of course value. With world-wide references, Buck Systems have developed an
outstanding reputation for quality and service, to become the clear leader in
contained materials handling / IBC Systems technology.
Key technologies and services include:
- Contained Materials Handling Systems
- Dispensary Systems
- Powder Handling
- Tablet Handling
- Container Blending
- Container Washing
- Plant automation
- Project Management and Validation
This article details some of the considerations required to specify and
select an appropriate contained materials handling system for a Generics
project and gives consideration to the increasing demands in regulatory terms
and especially with regard to containment.
Solid Dose Form Contained Materials Handling
Dispensaries
As a key part of any Pharmaceutical processing plant, the dispensing area
presents many challenges. In particular, it is important to establish a clear
understanding of both existing processes and products, and future requirements
as far as possible. Buck’s approach to some of the key issues for a dispensary
within a production based plant can be summarised as follows:
A dispensary can take many forms: single or multi level, low or high
containment levels, commonly incorporating two to four weigh platforms, a weigh
hopper, extraction equipment and sieving equipment. The dispensary may also
include recipe management software, waste disposal system and a method of
handling API.
Excipients and bulk ingredients arrive packaged in various forms, thus
requiring differing handling methods. For small volume dispensaries or line
dedicated dispensaries with a small batch size, the preferred method may be
manual. However, with ever more stringent manual handling regulations, it may
be necessary to add automation and mechanical handling to avoid these problems.
For larger volume plants and larger batch sizes, it is essential to automate
the handling. This is achieved by either simply lifting a pallet with a local
stacker truck, or ideally by using a hoist lifter. The advantage of the hoist
lifter is its ability to simply handle sacks, drums and bags without the
additional difficulties of manoeuvring in what is often a confined area.
Dust exposure is another key consideration. This obviously depends on the
types of products, local Health and Safety regulations and dispensary room
design. There are several ways to approach this issue, for example as
follows.
1. The traditional method is to rely solely on the room air changes and with
use of operator protection such as dust masks and air hoods.
2. An alternative approach is to establish an air curtain across the inlet
of the weigh hopper. This is a simple but very effective solution provided that
the equipment design and extraction levels are properly integrated.
3. Another alternative is use of an extraction hood above the weigh hopper,
enabling the operator to dispense ingredients within the extraction zone. This
provides additional protection, thereby ensuring a high level of safety, in a
cost effective manner.
4. Extraction booths and laminar flow booths are also often used, sometimes
in conjunction with the above solutions, to create an additional airflow away
from the operator. This extra protection offers improved flexibility in the
working area, although special airflow patterns may be required to ensure safe
airflow is achieved around the weigh hopper and any other equipment within the
booth.
5. For toxic materials, an isolator may be required, however the number of
isolators should be limited due to the comparatively high capital and operating
expenses. The use of contained charge vessels can significantly reduce the
requirement for isolators, especially when incorporated in the process plant
design.
The weigh system typically includes a bench top scale, floor scale and load
cells on the dispensing hopper. In addition there may be a weigh frame for
‘check weigh’ purposes. The weigh frame may be located on the same level, or
ideally, when charging Intermediate Bulk Containers (IBC), on the floor level
below. When filling the IBC on the lower level, it is also possible to
integrate the weigh frame into a post hoist to lift and dock at ceiling height,
although this can reduce system accuracy.
Sieving is common requirement and must be incorporated in the design of the
dispensary to ensure that suitable air flows and dispensary ergonomics are
achieved.
The API can be handled in several ways depending on the containment level
recommended by the plant Occupational Hygienist. For example, transferring the
required quantity of API into a contained charge vessel within an extraction
booth or dedicated isolator as mentioned above. This charge vessel,
incorporating a Buck® split-valve technology can be manually
moved safely
around the plant to enabling the API to be safely used at the ‘point of use’.
Furthermore, ideally the API can be transferred into a contained charge vessel
at the primary production plant, already prepared for dispensing at the point
of use, or for contained dosing, negating the need for an isolator.
Recipe management can be achieved in several ways; a paper driven system
requiring the operator to record all weigh dispensing operations, a simple
recipe display driven and paper based system, or a full SCADA driven system
guiding the operator through all key stages ensuring complete control and batch
data security in accordance with 21 CFR part 11 – Electronic Signatures and
Records. It is essential that a dispensary control system is practical for the
operator, e.g. use of bar code scanner with intelligent hand held displays to
assist in inventory management, limiting operator intensive tasks and improving
production efficiency.
Buck will normally supply the dispensary system as an integrated package
with the specification and design incorporating key issues such as:
cleanability, interchangeable weigh hoppers, ease of maintenance, building and
utility requirements, and all process requirements.
Solid Dosage Processing
After the dispensing of the ingredients into an Intermediate Bulk Container
(IBC), the IBC can be transferred to the next process step, where the method of
IBC discharge will depend on several key factors such as the product
characteristics, the facility design and the processes to be undertaken.
The product characteristics have a significant influence on the type and
design of IBC and discharge device to be used. Buck specialise in providing the
most advanced technology for transferring and containing powders, granules and
tablets. It is essential that the intermediate and active ingredients be tested
to establish flow, segregation and handling properties, in
order to select
the optimum technology for the project.
Where products are known to be difficult to discharge, or susceptible to
segregation, then Buck offer innovative technical solutions such as Vibroflow™,
and a full range of technical solutions for varied Occupational Exposure Level
(OEL) requirements (10-100 nano g/m³ through to 50 µg/m³ in various technology
steps).
Where a plant is to be designed for multi-product use, Buck often apply
their advanced technical solutions to ensure security of outcome, including
provision for future unknown products.
The building design has a key influence on the materials flow
philosophy.
Often existing buildings have limitations in height,
number of floors levels and access. These limitations must be recognised as
early as possible, to ensure that the Contained Materials Handling system (IBC
System) is custom designed to the site requirements. Similarly, it is also
essential for the system supplier to be involved at the initial design phase of
any new buildings. Key areas of influence can include the number of floors,
area classifications, material and
process flows and product charging
philosophy to the process equipment (described below). In addition, the number
of valve operations in each process area must be considered; e.g. these must be
limited for contained applications. The process flow can often be improved to
minimise the number and type of interfaces between each process step.
Significant project capital cost reductions can sometimes be achieved by
enhancing the equipment containment technology (say from 100 µg/m³ OEL to
typically 5 µg/m³ OEL) to reduce facility costs, by reducing the ‘white’ GMP
process areas to designated ‘grey’ areas.
Some of the key process areas to be considered at the process equipment
and plant design stages are listed as follows:
Granulation – Addition of API
With the use of contained
charge vessels it is practical to add active ingredients (API) into each
process step in a contained yet simple manner. Methods of interfacing with the
charge vessels have been established within tGEA Pharma Systems.
(Aeromatic-Fielder High Shear Mixers and Fluid Bed Dryers, Collette Ultima™
‘Single Pot’ Processors, Courtoy Rotary Tablet Presses and Buck Systems).
Milling – Reducing the Dust Hazard
System designs
incorporating containment valves will limit airborne dust, and may therefore
assist in reducing area classifications. It is also possible to improve safety
by using the containment valve interlocking features with a nitrogen purge
system. Using similar principles it is possible to improve the operational
conditions of a Roller Compacter.
Vacuum Charging – Room Height Restrictions
Where
possible it is best to avoid vacuum transfer because of cleaning, segregation,
contamination and dust exposure issues. Where this is not possible, for example
where room height constraints prevail, a similar approach to Milling can be
taken, by using a contained Vacuum Station. A typical application is charging a
tablet compression machine.
Mixing and Blending – Key process step
Increased
efficiency can be achieved by combining operations, e.g. integration of milling
and sieving operations, and the addition of tabletting lubricants using
contained charge vessels. Buck IBC Blending technology is completely contained
with the possibility of a technical maintenance area minimising the GMP process
area. With the Buck ‘Prism™’ it is possible to improve mixing efficiency whilst
maintaining containment, and prevent segregation during discharge using the
Vibroflow™.
Compression, Coating & Capsule Filling – Contained
Feeding Generally there are three main approaches to feeding a
tablet press, capsule filler or tablet coater; vacuum filling, direct charging
from an IBC using a hoist, or ‘through the floor’ feeding.
Vacuum filling
generally suffers from poor dust control and cleaning problems (as mentioned
above). Considerably more operator intervention leads to reduced efficiency,
and in addition, segregation can often cause quality problems.
Direct charging from an IBC is very effective for several reasons; it is
quick and efficient, it limits any segregation, prevents the risk of chute
blockages and simplifies any cleaning requirements. This does however require
transport of the IBC in and out of the process room. The use of a post hoist
(as oppose, for example, to use of a stacker truck) limits risk of damage to
the process equipment and enhances operator safety.
Direct charging from either a mezzanine level, or ideally from an upper
floor, offers a simple solution for handling an IBC, whilst avoiding the need
to enter the process area with the IBC and thereby reducing the process room
size. The segregation of powders can be avoided by
using Buck’s Decelerator
technology, which is designed to maintain area segregation, CIP or ‘quick
strip-down’ for rapid product change over. In addition, the upper floor can be
designated a ‘grey’ area. This approach is particularly effective for larger
plants with several discharging stations because of reduced overall capital
costs, with this benefit compounded by the smaller ‘white’ process area.
Tablet and Capsules Handling
It is arguable whether
containment can be reduced once the powders have been compressed into tablets,
or after capsule filling or tablet coating. This applies in particular to the
IBC valve technology. Consideration should however also be given to the value
of the finished
pharmaceutical product. Using stainless steel tablet
containers significantly increases security, and reduces the risk of damage
caused by spillage. The tablet IBC is washed after use in a contained manner.
Tubs or plastic containers can contribute to problems with storage, washing and
often add to ‘hidden’ operating costs. When transferring tablets and capsules
physical damage must be avoided. As with powders and granules, Buck’s
Decelerators will prevent such problems when feeding through floor levels. For
example, discharging after compression when feeding into a tablet coater or
packing line.
IBC Washing Systems
It critical to establish a cleaning philosophy for any new facility; this
will depend on the products, processes and production demands. A multi product
plant may look for quick changeover, where product dedicated plants adopt a CIP
approach where possible. When handling
hazardous or toxic materials CIP may
be preferable, but this may also be combined with a contained quick change over
solution. The cleaning philosophy is an integrated part of the design of the
materials handling system and should not be look at in isolation. It is
possible to
specify simple yet contained wash systems, ensuring the
operator is not at risk during cleaning.
Automation of IBC Systems / Contained Materials Handling System
The level of automation for a materials handling system requires careful
consideration. Under-specifying automated control can increase operator safety
risks, e.g. manually operating a containment valve above a rotary tablet press.
Obvious benefits of automation include; improved productivity and reliability
(even after allowing for the increased validation requirement), also leading to
reduced manning and operating costs.