By Louis Garguilo, Chief Editor, Outsourced Pharma
Ours is a responsive Editorial Advisory Board, but no question posed to them elicited the range and rate of response as this one:
“What are the biggest challenges you face with outsourcing fill finish services – what keeps you up at night?”
Chances are, many Outsourced Pharma readers are also experiencing the same challenges board members told us about, and I’ve listed below for you.
Some Defining To Do
Let’s begin, though, with some defining. For the most part, the biopharma industry uses sterile and aseptic fill finish interchangeably, but note this paragraph from Difference.Guru:
“So what is the difference between aseptic and sterile techniques? Aseptic techniques are used to promote asepsis, a condition that is clear from harmful pathogens, viruses, parasites, fungi, and harmful spores. Sterilization is the process of eliminating living microorganisms of all shapes and forms.”
Of course, different molecules and programs – and there are more variations today than ever before – call for different requirements. Here are two additional definitions, these this time from industry sources (click on titles for more detail):
Aseptic Fill & Finish: “Aseptic filling is an aseptic process that requires the close coordination and complex interaction between personnel, sterilized product, the manual fill/finish equipment system, cleanroom and support facilities (Class 10,000/Class 100), and sterilized filling components.”
Fill Finish Processing: “After upstream bioprocessing, [the] formation of the active agent by cell culture or fermentation, and downstream purification; this is when the final product has the greatest value, and, thus, the most to lose to a product failure … and any mistakes at this point can potentially lead to product misformulation, contamination or improper packaging.”
The Board Responds
I’ve done minimal editing to these selected responses from board members regarding the current challenges they are facing in outsourcing fill finish services, and working effectively with their external partners.
(1) The First five (Vimal Gandhi, AstraZeneca )
(2) Specific Challenges: Cell Therapy Field (Bernie Huyghe, Allogene Therapeutics)
(3) Specific Challenges: Antibody Drug Conjugates (Michael Mulkerrin, ADC Therapeutics)
(4) And About That Data (Anand Ekambaram, Merck)
(5) From The Consultants (Bikash Chatterjee, Pharmatech Associates; Peter Bigelow, xCell Strategic Consulting))
These challenges consistently creep up with fill-finish operations:
(6) More From Big Pharma (Todd Mabe, Merck)
Top 3 Challenges Revealed
What do we learn from these initial responses?
First, it’s apparent finding and booking the right Capacity for fill finish services is a challenge.
Second is the uncertainty around Annex 1. In December 2017, the EMA published “long-awaited” revisions, as described by GMP News, to guidelines for the "Manufacture of Sterile Medicinal Products" guidance, with public comment on those revisions having ended this past January. “The guideline published in 1971 had last been revised in parts in 2008. The present draft is the first complete revision of the guideline. Amongst other things, it was designed to pay credit to new issues like quality risk management as well as new technologies and procedures … While Annex 1 consisted of 16 pages since its last revision in 2008, the new document with its additions and changes now amounts to 50 pages…”
Third, and more tactically, shall we say, was concern about the continued reliance on visual inspection, as well as overall frustrations with analytical and testing. More automation, broader services capabilities, and much quicker turnaround are some of the needs here.
Thanks to the board for getting us started. Perhaps readers will add to this discussion. We’ve got more digging to do on both the client and provider sides to learn how we can improve fill finish outsourcing.