Regulatory assessments, especially in the domains of sterile formulations has always been stringent, and is ever increasing. With the advent of novel technologies, it is becoming increasingly interesting for the pharmaceutical industry to balance the two elements, such as continue to tread the compliance pathway, on one hand while incorporating advancements, on the other.
EMA has just released the draft for the revised, “Annexure 1” and “Guideline on the sterilization of the medicinal product, active substance, excipient and primary container” is in the draft stage for a long time. Once finalized, these two documents will represent the agency’s current approach to sterile formulations. 

The USFDA, in last couple of years, has released the question based review documents for microbiological quality assessment for sterile products, e.g. “Question-based Review (QbR) for Sterility Assurance of Aseptically Processed Products” and “Question-based Review (QbR) for Sterility Assurance of Terminally Sterilized Products”. These two documents require, the use of, “Quality by Design” principles in designing the microbiological attributes of the sterile formulations.
The United States Pharmacopeia(USP) meanwhile, had released a most comprehensive chapter on sterilization <1229>, “Sterilization of compendial articles”, containing seven sub-chapters.
Although these chapters are available for some time now, the complete impact on the product sterilization process development is yet to be adopted by industry.
The inspection trends from the FDA and the MHRA, for sterile formulations, offer a mixed bag of learnings, with a lot of changes in the way inspections were/are conducted, and observations were provided/are being provided by the agencies.
The presentation will deal with details on these regulatory guidance’s and the possible solution(s), utilizing a case study on pre-filled syringes.

Following the more frequent request for ready for filling containers, ISO TC76 published in 2015 the standards for sterilized sub-assembled ready-to-fill glass syringes ISO 11040-4 and ISO 11040-7, including the corresponding packaging system. These two standards define the production of the glass syringes and the related test methods, as well as the “ready for filling” packaging.

In November 2016, ISO TC76 published ISO 11040-8 Requirements and test methods for finished prefilled syringes.Due to the increasing market presence of syringes “ready for filling” and the associated advantages of this product for the pharmaceutical industry, the suppliers of packaging materials started to develop systems of this type for vials.

ISO TC76 is developing two International Standards to specify the characteristics of sterile and ready for filling empty glass vials and cartridges, including the minimum requirements of materials, the packaging systems and analytical test methods (ISO CD 21881 and ISO CD 21882).

ICG is a nonprofit GLASS SOCIETY comprising 33 national organizations in glass science and technology that promote cooperation between glass experts through its Technical Committees (round robin testing, publication of scientific & technical papers) and by assisting in the organization of conferences.

TC12 Pharma Packaging has the main general objective to support glass containers for pharmaceutical products in front of the demands of new drugs and new drug delivery systems and to identify R&D needs in this field.

The first objective of TC12 has been to set up an experimental method for the evaluation of the propensity to delamination. One of the major source of differences in results among the ten participating laboratories was the autoclaving cycle, set according to the E.P. and U.S.P prescription for the hydrolytic resistance testing.

TC 12 decided therefore to host on October 2017 at the University of Padua, a workshop on the autoclaving best practices inviting representatives from Glass Industries, Pharma Industries, Autoclave manufacturers and Independent Glass Laboratories.

The target was to promote a constructive discussion on this important topic and to produce a common document to be shared with Pharmacopeiae Authorities (E.U. and U.S.).

The scope of this presentation is to show the results and the outcomes of this important meeting in order to improve the reliability of compendial autoclaving testing.

The FDA Draft Guidance “Container/Closure Systems for Packaging Human Drugs and Biologics” was issued in 1999.  But in the past decades, there has been a change in the scrutiny of the way FDA reviewers looked at E&L data.   They have gradually increased the requirements, not backed up with any official document (Guidance, guideline…) which left the Pharmaceutical Industry in the dark, second guessing of what the current position and requirements were of the FDA to support a submission.

In this presentation, the key factors of success of any given E&L project will be highlighted.  Crucial is to understand what regulators really want and aligning the design space of an E&L study to their expectations.

Facing the reality of the ever-evolving regulatory landscape, analytical testing labs need to be on the forefront with expertise in the field of extractables and leachables testing and state-of –the art technology.  Meeting the development needs and requirements, of the pharmaceutical and biopharmaceutical industries, also raises the bar for material suppliers.

Only through successful partnering between drug product vendors, material suppliers and the CRO performing the test, a true mitigation of the risk related to packing can be established. 

High-end biotech products continue to enter the market posing new technical and regulatory challenges for the development of injection systems. Primary packaging for parenteral is exploring new materials and new technologies around all the typical themes involved with these systems: drug product and container closure system interaction, functional performances, mechanical performances and stability during time

In this presentation we are going to share how Stevanato Group can help to work around the different challenges through innovative primary packaging solutions for marketed and new biologic drug products.

In addition to that we would also introduce the SG4D capabilities that can further improve the help that we can give to the industry especially in the field of device primary packaging integration.

Datwyler is dedicated to guaranteeing the highest level of quality and safety and continues to make investments aimed at meeting the ever-stricter regulatory requirements of the industry. The highest industry demands are met with Datwyler’s most advanced manufacturing standard: First Line.

The FirstLine standards comprise a manufacturing concept for high-quality elastomer components based on ultra-modern clean room technology, automated production cells, fully automated camera inspection and a unique washing process. The FirstLineTM facilities are specially designed to manufacture pharmaceutical rubber components in a fully integrated good manufacturing practice (GMP) environment conforming to the highest industry standards. This innovative approach to manufacturing exceeds the most stringent quality standards of the European and US regulatory authorities and is certified to ISO 15378.

Datwyler chose Pune as the location for the new facility because of its strategic location and economic

importance for the region. India’s pharmaceutical and biotech markets are evolving rapidly and have been able to gain traction from global manufacturers, suppliers and customers. The country is also getting recognised as one of the global manufacturing destinations. The First Line aligned facility in Pune plays a substantial part in Datwyler’s efforts to cater to regional and global markets.

Elif Asani

Automatic Filling and Stoppering machine for ready to use Components The presentation will focus on Sterile Filling Operations in Nest, and will start from small batches to higher batches productions.

Our solutions for nested components (PFS/cartridges/vials) include Automatic Table Top Filling Machines and Automatic Filling Machines with higher speeds.

The presentation will then show details of the various operations in an automatic high-speed machine:

• De-Bagging and de-lidding operations
• Transfer to filling/stoppering machine
• Filling process and options available
• Rubber bung application by vacuum
• Nest exit
• capping operations of vials

We will also give an overall view of O-Rabs/C-Rabs with focus on Isolators that will be presented by our partner.

Presentation will include drawings, pictures and where possible videos.

Mirko Tassinari

Isolators for aseptic filling and stoppering of ready to use primary packaging.

The presentation will focus on custom designed isolator to enclose the filling, stoppering and capping operations of a liquid or powder filling machine while providing an aseptic and safe environment for the process.

Comecer solutions for automatic machine (from small batches to higher batches productions) include positive or negative pressure isolators, Hydrogen Peroxide decontamination system, viable & non-viable monitoring system and automatic glove leak test.

The presentation will then show details of Comecer’s isolators in an aseptic high-speed filling machine:

• Ergonomically designed
• Positive pressure unidirectional airflow system with HEPA inlet and outlet filtration,
• Special “mouse hole” protected by unidirectional airflow for exit of filled vials and syringes
• Integrated Hydrogen Peroxide decontamination system

Presentation will include drawings, pictures and where possible videos.