In 2003, PDA published the paper, "Points to Consider for Aseptic Processing" as a commentary on the then draft U.S. FDA guidance on GMPs for aseptic processing (1). Since then, there have been considerable changes within the industry resulting in additional knowledge, including new regulatory guidance in this area. Due to this increase in expertise, PDA has set up a task force comprised of experts in several areas to revise this document.
This revision also comes at a time when regulatory authorities are updating or developing regulations and guidelines in the area of sterile manufacturing, such as Annex 1 of the European GMPs. PIC/S also established a working group in this space as well in 2014. According to Gabriele Gori, Global Head GMP Compliance and Auditing, Novartis Vaccines and Diagnostics, the task force believes that the revised Points to Consider document may be of interest to those regulators working on these GMP initiatives.
"We felt after 11 years it was time to revise this PDA document to consider the new technologies, the new approaches," Gori said at the Parenterals conference in November in Munich. "We also noticed that by working on this Points to Consider document this may also be useful, possibly, for regulators for their revision of Annex 1 or any other guidance or standard."
The basis for the revision lies in five related regulatory goals: 1) Use of science and risk-based approaches; 2) Application of modern technology; 3) Reevaluation of traditional control strategies; 4) Consideration of new product/container presentations; and 5) Harmonization of global regulatory expectations.
Gori stressed how important harmonization is, "specifically, for people like me who on a regular basis deal with different regulatory authorities from different parts of the world. So, all the science is the same everywhere, so we really hope to come to some common agreement as to what are the requirements."
The task force hopes the revised PDA Points To Consider addresses specific areas in need of clarification, reflects current state-of-the-art practices, and supports the effort to revise the current Annex 1. "We truly believe that only with open communication with experienced professionals and, in particular, between regulators and industry can we really achieve the target, which is a common target for us and regulators because we are all trying to get the best out of this for the interest of our patients."
Some of the topics included in the revision are airflow velocity and patterns, unidirectional flow versus laminar flow, grade A environment over cappers, differential pressure, testing of HEPA filters and HEPA filters patching, tube length and bend radii for total particulate sampling, monitoring of ≥ 0.5μm and ≥ 5.0 μm particles and room classification, environmental monitoring alert and action levels setting, location and frequency of monitoring of total particulates and viable particles, sterilizing filter integrity testing, and more.
Currently, the Points to Consider revision is still in process and has not yet been approved by the Science Advisory Board or the Board of Directors.
- "Points to Consider for Aseptic Processing." PDA Journal of Pharmaceutical Science and Technology 57, no. 2 (2003).
About the Expert
In his role, Gabriele Gori provides oversight into the GMP Compliance status of all the Novartis Vaccines and Diagnostics facilities worldwide, and coordinates the divisional auditing team which is in charge for the assessment of Novartis Vaccines facilities and for the evaluation and monitoring of third parties and critical suppliers. He is also the chair of the Novartis Sterility Assurance Expert Network (SAEN), which provides guidance to all Novartis divisions on Sterility Assurance matters.
Points to Consider in the Manufacturing of Sterile Products Revision Task Force
- Hal Baseman, Valsource, Co-chair
- Gabriele Gori, Novartis, Co-chair
- Masahiro Akimoto, Toray
- Marc Besson, Sanofi
- Jette Christensen, Novo Nordisk
- Veronique Davoust, Pfizer
- Vincent O’Shaughnessy, Amgen
- Phil DeSantis, Consultant
- Richard Johnson, PDA
- William Miele, Pfizer
- Janie Miller, PDA
- Rainer Newman, Consultant
- Michael Sadowski, Baxter
- Edward Tidswell, PhD, Baxter