Process characterization (PC) studies are experiments performed primarily at laboratory scale to demonstrate process robustness and provide data necessary for planning, risk mitigation, and successful execution of process validation (
1
,
2
). These typically involve extensive, multifactorial testing designed to determine the effects of operational parameter perturbations and raw materials on process performance and product quality (
1
,
2
). Product-specific information from development studies may be used to help guide PC study design; however, such information may be limited or insufficiently substantiated before PC begins. PC studies thus may include many operating parameters that ultimately have little or no process impact but are included in PC study designs because prior knowledge is lacking. In addition, most design of experiments (DoE) used for PC are powered to identify two-way interactions, which may be rare or have no significant process effects.
Recent guidance documents highlight a regulat...
The year 2011 may be seen as one in which regenerative medicine entered its adolescence. Public attention — from investors to desperate patients — finally turned toward this nascent industry with something other than skepticism or unrealistic expectations. The FDA’s approval of Dendreon’s Provenge cellular immunotherapy switched on the spotlight, and cell therapy companies suddenly faced a barrage of questions about cost, manufacturing issues, product development, and patient access.
US Policy:
In May 2011, US representatives Brian Bilbray (R-CA) and Diana DeGette (D-CO) introduced the bipartisan Regenerative Medicine Act of 2011 (HR 1862) in the US House of Representatives. Major provisions include creation of a multiagency Regenerative Medicine Coordinating Council within the Department of Health & Human Services (HHS); establishment of grant programs to accelerate the availability of life-saving regenerative medicine therapies and research tools; funding of critical regulatory research at the Food & D...
Mathematically modeling the kinetics of batch and continuous cultivation allows you to not only calculate and evaluate the effects of process parameters, but also to forecast those parameters and duration of cultivation to develop a cost-effective production process. Mathematical modeling microorganism cultivation was intensively developed in the second half of the last century.
Equations 1–6: ()
Monod proposed
Equation 1 for batch processes in 1942 (
1
). In that equation, µ and µ
max
are the specific and maximum growth rates, respectively (h
−1
),
S
is the substrate concentration, (g/L), and
K
S
denotes a Monod semisaturation constant (g/L). That model implies that yield
Y
is a constant value. For continuous-mode cultivation (e.g., chemostat),
Y
can be calculated using
Equation 2, in which
X
is the biomass concentration (g/L), and
S
0
is the limiting substrate concentration in the input (g/L). For a continuous cultivation at flow rate
D
(h
−1
), combined solution of
Equations 1 and
2 give...
Host cell proteins (HCPs) can be present in significant amounts in biological products through copurification with a recombinant protein-drug substance. Purified active ingredients developed for human use must be free of all contaminants — including residual HCPs — to minimize the incidence of immunogenicity against a drug product or its trace contaminants (
1
).
HCP assays allow for monitoring host-related impurities during product development and process development. Most are in the enzyme-linked immunosorbent assay (ELISA) format for detecting complex mixtures of proteins and allowing for a reasonable estimate of HCP mass in a drug substance. HCP limits have not been set by regulatory agencies. They are determined case-by-case depending on drug dosage, route of delivery, dosing frequency, and so forth. However, most HCP levels are 2).
PRODUCT FOCUS:
PLANT-DERIVED HUMAN BIOLOGICS
PROCESS FOCUS:
DOWNSTREAM PROCESSES AND PURIFICATION
WHO SHOULD READ:
ANALYTICAL PROTEIN/PROCESS SCIENTISTS, QA/QC
KEYWORD...
+5Ultrafiltration (UF) is a membrane-based separation technology commonly used in the biopharmaceutical industry for concentration or diafiltration of protein solutions to remove low–molecular-weight (LMW) impurities or exchange buffers. The nominal MW limit of UF membranes ranges from 1,000 Da (1 kDa) to 1,000,000 Da (1,000 kDa). A target product is retained by the membrane while lower-MW solutes or impurities pass through (
1
). For a target product with a smaller MW than the impurities, separation is accomplished by allowing the product to pass through the membrane into the permeate side instead.
One key factor that influences robust and successful operation of an ultrafiltration process is integrity of the membrane assembly. An integral membrane system is required not only for achieving desired product yield and purification during process operation, but also for ensuring process consistency and adherence to good manufacturing practice (GMP) guidelines across multiple batches during a production campaig...
+1 In bioprocess development, small-scale systems are used to identify appropriate cell lines, media, and feeds before applying more expensive, controlled cultivation systems at larger scales. Process development relies on data generated in such uncontrolled small-scale cultivation systems, so comparability is an issue.
Shake flasks are commonly used for small-scale culture of mammalian suspensions. Incubators provide a suitable environment with carbon dioxide (CO
2
) supply and humidity control and ensure sufficient oxygen transfer and homogenization of cell suspension by appropriate mixing. To match scale-up parameters, users can adjust power inputs by changing the shaking frequency and eccentricity of the shaking movement or by modifying the working volume of the shake flasks. No reliable system for automated feeding and sampling at shake flask scale is yet available, so it is necessary to take flasks out of their incubator to do so. Such disturbances can affect the metabolism and overall performance of c...
+2 3D Bioreactor
Product:
InBreath whole-organ bioreactor
Applications:
Tissue engineering and regenerative medicine for trachea, esophagus, intestines, blood vessels, and other hollow, tubular organs
Features:
The autoclavable, GLP-compatible InBreath bioreactor is designed for cell seeding and culturing on intraluminal and extraluminal surfaces of a tubular matrix. A polymer culture chamber houses the scaffold and culture medium for the entire duration of organ generation. Secondary “paddle” elements move with the scaffold holder to mix the culture medium continuously for mass transport and oxygenation. The scaffold construct rotates by a motor that is completely separate from the culture, with a detachable connection.
Contact Harvard Apparatus
www.harvardapparatus.com
Sterile Disconnection
Product:
Kleenpak sterile disconnectors
Applications:
Single-use fluid management
Features:
Kleenpak sterile disconnectors are designed to maintain sterile integrity (even in cramped and uncontrolled environment...
The vast majority of drug shortages — 82% of the 168 products in short supply — are sterile injectables. According to an IMS Institute for Healthcare Informatics report from November 2011, many are linked to fill– finish deficiencies. In addition to supply shortages, medicines can be delayed in reaching patients due to contaminated raw materials, findings of particulates, extractables and leachables, vial stopper and glass problems or interactions with product, and even cross contamination.
IBC’s Drug Product Quality Summit is the only event that focuses on all those nightmares — and how you can prevent them from coming true. The program focuses on hot-button issues that have cost the industry millions of dollars from FDA Form 483s, clinical holds, and lots rejected because of quality problems. This is the one event at which quality, technical, and regulatory professionals can quickly learn about the most recent failures and findings that have caused drug shortages, plant closings, and expensive product l...
The role of patients in changing the pharmaceutical industry’s research agenda is evolving. Patients are greatly affected by drug R&D, with its potential to provide cures or treatments for a wide range of different medical conditions. But new product development does not always meet all patients’ needs. For example, drugs for Parkinson’s disease most often aim to treat movement disorders, whereas patients are also concerned about pain, sleep problems, lack of bowel and bladder control, and sexual dysfunction (
1
).
Some organizations have always included patient perspectives in their research. For example, the Cochrane collaboration (an international network of academics and clinicians who carry out systematic reviews of evidence about treatments) has always believed in equal partnerships among researchers, providers, practitioners, and patients. And the James Lind Alliance (a nonprofit initiative) was established in the United Kingdom in 2004 to bring together patients, care providers, and clinicians who...
