UA-44035381-1

Extractables MDI PES Membrane Capsule Filters as per BioPhorum Operations Group (BPOG) Protocol

As per the Standardized Extractables Testing Protocol for Single Use Systems in Bio manufacturing proposed by the BioPhorum Operations Group (BPOG) Extractables Work Group, "General requirements for extractables and leachables (E & L) are already mandated by regulatory agencies. Biopharmaceutical companies must meet these requirements in demonstrating equipment suitability and GMP compliance whether the equipment is of traditional design or single-use. However, because of the absence of specific regulatory requirements for extractables testing of Single Use Systems (SUS) components, companies have needed to generate SUS extractables testing methods by extrapolating from their interpretation of regulatory requirements for existing container closure testing methods".

Although SUS Suppliers provide some data on extractables of various SUS components, which is generated through varying study design as there are no industry standards available for such studies, it does not represent the full range of process conditions encountered by SUS components. Also, such non standard methodologies pose a challenge to the bio-process owner with regards to interpretation and comparison of extractable data from different suppliers.

GCMS

It highlights the need for a standardized approach to establish extractable from different single use system (SUS) components which helps:

  • Ensure the manufacturing systems do not adulterate the final product
  • Avoid same components being tested multiple times and delay in applications of SUS in bio manufacturing
  • Minimize the time consuming process of bio pharmaceutical companies to conduct their own studies
  • Demonstrate product compatibility, process performance and fitness of the functional design for its intended purpose

The protocol, based on full range of conditions encountered by SUS components during use, proposes a detailed study of extractables from a given SUS component with a wide range of extraction solvents at multiple time points under dynamic conditions at different temperatures.

HPLC

Extractable Study: MDI Polyethersulfone Membrane Capsule Filters

MDI sponsored a full scale extractable study of Polyethersulfone membrane capsule filters as proposed in the BPOG protocol for extractables.

mdi AseptiCap capsule filter is a dual layer PES membrane capsule filter with support layers, plastic components i.e end caps, inside core, outer sleeve, capsule filter housing along with Inlet/ Outlet connections. The potential sources of extractables include membrane components,support layers and plastic components and the extratables could be plasticizers, antioxidants, residual solvents and surface active agents. Since the level of filter extracts migrating in process streams is relatively low, highly sensitive instrumentation is used to detect, identify and quantify the same for their assessment.


Extraction

The study was carried out on two different lots of gamma sterile PES membrane capsule filters and the extracts were prepared with six different extraction solvents under specified dynamic conditions for three different time points at different temperatures.

Preconditioning

In order to simulate worst case conditions: 

  • The capsule filters were gamma irradiated @ 50 kGy and the extractions were prepared within 5 weeks of gamma irradiation.
  • Also, though flushing of filter prior to use will significantly reduce the filter extracts in the process stream. The test filter was not flushed prior to performance of filter extraction study.
Extraction SolventTime and Temperature
<30 min(Ambient 25°C)24 hours(40°C)7 days(40°C)
50% Ethanol
1% Polysorbate 80
5M NaCl
0.5N NaOH
0.1 M Phosphoric acid
WFI

Analytical Techniques

Various analytical techniques were used to identify and quantify the filter extracts. ICP- MS (Inductively Coupled Plasma Mass Spectroscopy) was used to analyze trace amounts of targeted elements. Liquid Chromatography Mass Spectroscopy (LC-UV-MS) and Gas Chromatography Mass Spectroscopy (GCMS) techniques were applied to detect diverse (Non volatile, volatile and semi volatile) extractables. Alternate sample introduction techniques (head space analysis) and detectors (flame ionization detector) were used to increase the range of detectable extractables.

Analytical TechniquesTarget Extractables
Inductively Coupled Plasma Mass Spectroscopy (ICP- MS)Inorganic compounds
Liquid Chromatography Mass Spectroscopy (LC-UV-MS)Non volatile organic compounds
Gas Chromatography Mass Spectroscopy (GCMS)Semi-volatile and volatile organic compounds
Head Space Gas Chromatography Mass Spectroscopy (HS-GCMS)Volatile organic compounds

A detailed report on the extractables study is available on request. For more information, Please contact: info@mdimembrane.com