Also the place and date of birth, use in production, incidence and course of disease and final disposition should be recorded for each production animal. Viruses also present a significant potential safety concern to patients. The stages of cell growth should be described in detail including the selection of inoculum, scale-up for propagation, and established and proposed if different production batch size. Manufacturer A list of all firms associated with the manufacturing and controls of the drug substance, including contract laboratories for quality control and stability testing. The Use of Living Recombinant Organisms Biopharmaceuticals are the result of applying genetic engineering to living cells, whether it be bacteria cells, yeast cells, mammalian cells, viruses, whole animals or whole plants. Expansion of the Recombinant Organism 159 The production process for a biopharmaceutical at an early clinical stage will be basic and somewhat unpolished. A recognition that quality cannot be inspected or tested into a drug product 57 58 Chapter 4 2.
. This should be performed for either nucleic acid or protein sequence methods. The first principle is that salts are preferentially excluded from both protein surfaces and chromatography resins. For this reason, these banks will need to be regenerated over time, with controls to ensure that the fidelity or yield of the expressed biopharmaceutical product is not impacted. Physicochemical Characterization of Reference Standard and Qualifying Lots b.
Validation data and established specifications ordinarily need not be submitted at the initial stage of drug development. Process gases and water are considered raw materials. Having tight release specifications gains little if there is low confidence in the analytical methods used to generate the data. Definitely one of the best I have ever attended. In most cases, information on component ranges is not necessary. Coley endured decades of derision from the American Chemical Society.
Monitoring of Growth Parameters It is important for a bioreactor system to be closely monitored and tightly controlled to achieve the proper and efficient expression of the desired product. How Much Change is Acceptable? A detailed description should be provided of the cloning process which resulted in the final recombinant gene construct. Air in purification areas should be monitored for viable and nonviable particulate quality during dynamic conditions. Indication should be made as to the multi-use nature of areas and equipment e. Regulatory Expectations During Clinical Development 267 5.
The number of generations should be clearly defined for elite, transgenic and production plant lines with reference to the documented genetic stability of the process. The plan should include monitoring techniques, endpoints, and methods of reporting results. Virus Safety Calculation 195 7. Five Major Areas Involved in Validation of the Production Process 130 3. A restriction enzyme digestion map indicating at least those sites used in construction of the vector should be provided. Adventitious viruses are unintentionally introduced viruses. Quality control record discrepant information included, but was not limited to the following: tests were performed but were submitted as not performed; missing raw data, test records and stored test results; calculation errors, transcription errors, rounding errors; and failures to perform repeat testing as required after test control failures.
In general, deficiencies in documented history may not, by itself, be an impediment to product approval, but extensive deficiencies will result in increased reliance on other methods to characterize the cell substrate. A complete description of the analytical procedure and supporting validation data should be available on request. Appropriate and Sufficient Characterization 102 4. Characterization of a Gene Therapy Biopharmaceutical 239 3. Stability Stability of the reconstituted solution, when applicable, should be studied and data provided.
Differences between testing requirements for biologics versus chemical drugs will be highlighted. Optimal mixing ensures effective oxygen transfer, heat transfer, and dispersal of materials. The Art of Setting a Specification 258 4. These living hosts can provide an opportunity for amplification of various types of adventitious agents e. Transgenic plants such as corn and tobacco produce biopharmaceuticals in the kernel or leaf, respectively. The value of these biotechnology-derived drug products to improve patient health is widely accepted by the public. Through means of the internet, anybody can now download these documents for review from anywhere and at any time.
Attach connection for glucose, antifoam and alkali. Some manufacturers have even designed their production facility for multi-host concurrent manufacturing. Protecting the Gene Pool 151 4. Misuse in the Clinic 284 7. Consideration should be given to monitoring feed for pesticide residues. Test Method Validation - How Much and When? The facility could be for single-product manufacturing or for multi-product campaign manufacturing or for multi- product concurrent manufacturing.