APR Nov/Dec 2022 - 30

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FORMULATION AND DEVELOPMENT
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for a particular dosage form, those CDMOs will help guide the drug
manufacturer to make the right decision. It is equally important to
continue building the relationship in earnest with CDMOs to define
tasks and deliverables to achieve the long-term goals, in general.
Sterilization and Aseptic Processing
Sterilization is a key step in the manufacturing process to ensure that
pharmaceuticals and biopharmaceuticals are safe to use.5
General Considerations for Selecting a
Partner for Sterile Products
The key
parameters considered during sterilization are temperature, time,
and pressure to minimize the bioburden assay. Other parameters
are holding time between vial/bag filling and sterilization. The hold
time depends upon the media used; for instance, saline for injection
could be held longer than dextrose in water due to the possibility of
microbial growth and increasing bioburden. Terminal sterilization of
drug products is often carried out at 121°C for 15 minutes but if the
API is sensitive to higher temperature, the moist heat sterilization can
be conducted at lower temperature (ca. 115°C) for a longer duration or
opted for sterile filtration, if required.
Aseptic processing is a process that
involves careful and well
controlled engineering for the equipment used, facility, and
assemblies including the filling stations and chambers, and closures
of the vials or bottles to prevent any unwanted consequences of
batch failures and compromise quality risks. In most cases, human
borne contaminants are most critical and require immediate control
to mitigate the risk factor in aseptic processing.6
Regulatory guidelines are recommended for drugs in closed aseptic
container systems to reduce the risk for cross-contamination with
microbes that could lead to possible batch failures. The manual
sampling is also a cause for cross contamination, and therefore, the
FDA is advocating for closed single-use sampling systems.7
European
agency recommends that the bioburden should be monitored
before sterilization and the working limit on the efficiency should be
defined before the sterilization.8
In addition, the sterilization of drug
products in premixed bags requires further scrutiny by the agency
to confirm that no leachables or extractables are generated during
terminal sterilization.
There are two ways for achieving sterilization, one in which the
products filled in the containers are sterilized and second, the drug
product is preferably sterilized before filling under aseptic processing
conditions to avoid any cross contamination. Cundell reviewed the
justification for use of aseptic filling for sterile injectable products and
compared with terminal sterilization using moist heat conditions.9
A
better and more efficient sterilization can be achieved by terminal
sterilization only if the compatibility, physicochemical stability and
packaging and storage of products and suitability of delivery systems
are met for APIs and excipients. Unlike terminal sterilization, aseptic
sterilization can be widely applicable to all products highly sensitive
to higher temperatures, as a result the API's degradation can be
minimized, and stability can be maintained.10
It is widely practiced
within the guidelines set forth in the FDA's aseptic processing manual.11
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As sterile manufacturing demand continues to rise and remain strong,
CDMOs continue to expand their capacities by investing in highspeed,
latest isolator manufacturing technology with fully automated
packaging lines. Ascendia, like other CDMOs, has been expanding its
footprint in sterile manufacturing capabilities by providing services to
emerging and specialty and biopharma companies requiring cGMP
manufacturing from pre-clinical tox studies to first-in-humans (FIH)
and late-stage clinical batches as shown in Table 2.
With proprietary platform technologies in long-acting injectables, lipid
nanoparticles, or nanoemulsions for complex therapeutic modalities,
Ascendia's capabilities are at the par.13
Ascendia's cGMP manufacturing
capabilities, for example, include oral liquids, capsules and tablets, and
sterile injectable dosage forms for Phase 1 and Phase 2 and Phase 3
clinical supplies with commercial launch readiness by Year 2023.
Ascendia's capabilities and commitments to B.E.S.T. customer service
principles (brilliant technology, excellent service, superior quality and
trust), therefore, can bring the innovative molecules to human trials
faster, leading to expeditious commercialization of drugs for its clients.
Ascendia's most advanced aseptic fill stations include ISO qualified
clean rooms and isolators, to fill up over 9000 vials per hour with
Key considerations in identifying the right CDMO partner
require a level of mutual understanding about the scope of
work (SOW). CDMOs with innovative technologies, for instance,
have generated the opportunities with the clients interested in
aseptic manufacturing of sterile products, providing assurances in
formulation development and overcoming the challenges to deliver
high quality medicines for temperature sensitive APIs. In cases where
APIs are thermally stable in containers and packaging, sterilization
by steam or moist heat or irradiation is an option for preventing
contaminants from microbial growth or microbes. On the other
hand, APIs sensitive to higher sterilization temperature, the aseptic
filling is ideally used to maintain the sterility of all components.
Lyophilization of certain molecules could further improve the
stability of drug products that aid in storage, shipment, and shelf
life of drug products. Thus, a CDMO with enabling capabilities in
lyophilization and sterile fills through aseptic processes, can offer
services to clients working on small and large molecules and
biologics as well. A one-stop-shop CDMO, having the integrated
lyophilization and aseptic manufacturing capabilities under cGMP
that meets the ISO 5, ISO 7 and ISO 8 classifications as shown in
Table 1, can further expedite the development and marketing of
drugs faster.
Ascendia's Capabilities in Formulation
Development and Manufacturing of
cGMP batches
APR Nov/Dec 2022

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