This is the second part of the article covering section 8 and here we are looking at the requirements around Form fill seal and Blow fill seal.
The 2008 Annex introduced the concept of blow fill seal in a limited way. It was two clauses under the clean room and clean air devices section and as such gave only the barest of guidance. In the new Annex 1 we see much more including the introduction of Form Fill Seal.
In combination with the glossary, Annex 1 defines Form Fill Seal (FFS) as an automated process typically used for Terminally Sterilized product where a primary container is made from a continuous flat roll while filling the formed container with product and then sealing it. Blow Fill Seal (BFS) is similar and is defined as a technology in which containers are formed from a thermoplastic granulate, filled with product, and then sealed in a continuous, integrated, automatic operation. In the case of blow fill seal, the two most common types of machines are the Shuttle type and the Rotary type. Blow fill seal is more commonly linked to aseptic processing although in practice they can be used for either.
When considering the environmental conditions needed for operating FFS or BFS Annex 1 refers to certain generic requirements. For terminally sterilized products, BFS processes can be operated in a grade D environment. FFS processes however, need to operate in a grade C environment. In the case of an aseptically filled product using BFS, the point of fill needs to be Grade A with a background designed to ensure the grade point of fill is maintained. This allows for some flexibility. For example, the BFS machine can be in a Grade C environment provided the operators maintain a Grade A/B dress code. The reasons for this are simply that protection offered by BFS is greater than traditional filling. As seen in previous articles the same principle is applied to isolators i.e., Grade A, in a grade D, C, or B depending on the process. FFS aseptic filling processes follow the traditional grade a with B background.
Considering the FFS process in more detail, contamination of the critical packaging films should be minimized during component fabrication, supply, and handling. On receipts, checks should be for dimensions, integrity, and artwork.
About the author
Andy Martin
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this, he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
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FFS and BFS share similar controls that are identified during qualification. Some examples of differences for FFS include control of packaging films, requirements for film decontamination or sterilization and equipment cleaning-in-place and sterilization-in-place, as necessary. Process knowledge is essential so that process parameters are understood, validated, controlled, and monitored appropriately.
Critical Process parameters for routine monitoring, in addition to BFS include for example, settings for uniform package dimensions and cutting as well as setting, maintenance and monitoring of forming and sealing temperatures times and pressures. Others include environmental and product temperature and batch-specific testing of package seal strength and uniformity.
For BFS processes, polymer granulate contamination should be controlled by good design and maintenance of polymer granulate storage, sampling and distribution systems. The sterility assurance capability of the extrusion system should be understood and validated. The filling procedure defines the critical interventions that cause the filling process to be terminated. Specific BFS controls include for example, integrity testing of the product filling lines and filtration systems as well as polymer granulate, distribution systems and extrusion temperatures.
Critical process parameters for BFS include for example the setting, maintenance, and monitoring of extrusion parameters, as well as molding temperatures and rate of cooling. They should also include parameters for cleaning, sterilization & monitoring of critical extrusion, transfer, and filling areas where relevant. Furthermore, process parameters should include batch-specific testing of package wall-thickness at critical points of the container. In some cases, embossing may be required therefore parameters for the embossing setting are needed to ensure that unit integrity and quality is not compromised in the embossing process.
The Environmental control and monitoring programme should utilize air flow visualization to understand complex airflows from equipment and heat generation. Other factors considered include air-filter configuration and integrity, cooling systems integrity, equipment design and qualification. Critical zone monitoring is unlikely for rotary-type BFS because of the restricted space available compared to shuttle type BFS.
For both FFS and BFS any product contact gases should be appropriately filtered. There should also be procedures to detect and rectify sealing problems. Maintenance and tooling inspection plans should be risk based and where potential product quality concerns are identified they should be documented and investigated. Changes to container mould tooling should be assessed for risk to finished product container integrity.
About the author
Andy Martin
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
Training courses on Annex 1
There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
