Clinical manufacturing

Drug product manufacturing process poorly understood Development of clinical manufacturing process and its... 

Phase II Clinical Manufacturing Challenges with Standardized Formulations... 

The differing circumstances under which a validation study is prompted often dictate the best approach to be used. Agreeably, prospective validation, for which the validation studies are all completed and approved before shipment of any product, is preferred. There are however, opportunities to complete certain validation studies when producing product intended to be administered to patients. Such circumstances may arise during clinical manufacturing, when exten-... 

This approach would seem to be an example of concurrent PV [14], which fits well when the development function continues its effort to validate clinical manufacturing processes. It is also an opportunity to validate a process when it is used to produce different batch sizes with a given piece of equipment. It may even be possible to employ differently sized equipment (to make different batch sizes) as part of the validation effort. It remains to be determined whether this kind of approach ought to be extended to the commercial validation effort. Later in this chapter I will discuss the possibility, which should be attractive for the company that is totally involved in TQM. 

Scientific disciplines (e.g., Toxicology, pharmacology, pharmacokinetics, clinical, manufacturing) The areas that provide necessary scientific support. 

Fig. 2.2. Clinical manufacturing processes. (A) Upstream processes include raw materials qualification, cell expansion, transfection, and harvesting. (B) Downstream processes include cell lysis and clarification, chromatography, and filtering, vialing, and storage. Recoveries are indicated for each step.

The second component of a successful clinical manufacturing program is appropriate quality assurance systems for the production of cell or viral banks, raw materials, in-process materials, and final product. Much has been written about the production and testing of cell and viral banks for use in manufacturing. Both FDA guidelines and other reference information are available (http // www.fda.gov.cber/guidelines.htm http //www.ich.org, http //www. emea.eu.int). The production of AAV vector batches for use in clinical trials should use qualified cell, viral, and/or plasmid banks as appropriate. Documentation on the source materials for these banks is also crucial in assuring the quality and safety of the clinical trial materials. 

Fig. 3 shows a pilot plant layout with restricted personnel access. This design would support the development and clinical manufacture of solid dosage forms, liquids, semisolids, aerosols, and sterile products. Multipurpose rooms are incorporated in each area to maximize the use of portable equipment, and scale factors similar to those shown in Table 1 are employed. Isolation suites are indicated in the manufacturing area their purpose and design are discussed in more detail later. The sterile area is isolated from the main corridor by the interior corridor design. At the far left, the main corridor provides access for future facility expansion, if necessary. 

The building and operating costs can often be justified based on the direct costs of product development and clinical manufacture under contract. In addition, delays in clinical programs can cost the company millions of dollars in lost revenue. However, if building or operational costs carmot be justified, it may be more effective to outsource work to a This may... 

The system must provide the ability to print various inventory, sample, and pre- and post-dispensing labels. All labels should include a bar code and printed text with the pertinent batch and/or lot information. Labels must comply with GMP-GLP (good laboratory practices) requirements to meet the needs of both laboratories and clinical manufacturing. Labels should be available in multiple sizes to accommodate laboratory sample containers as well as production drums. 

In the small-scale clinical manufacturing phase, formulations are manufactured under GMP conditions for possible clinical testing. These will be manufactured on a larger scale than those in the previous phases. Anexperimental design is chosen however, if some of the variables can be eliminated based on the earlier experiments, the number of formulations produced may be reduced. 

To gain buy-in and input from all the key functions at the start of development (such as Pharmaceutical Development, Safety, Clinical, Manufacturing Operations, Quality Assurance, Regulatory and Marketing)... 

POC) studies. In addition, the HKBll expression system can be used to develop cell lines for stable production and clinical manufacturing of biopharmaceutical prod-... 

If stability information is no longer needed, the smdy could be cancelled. Appropriate approval must be secured in order to cancel a study. An SOP must define the authority needed to stop the testing. Depending on the nature of the study, departments such as clinical, manufacturing, QA, or RA would need to be part of the team that cancels a stability smdy. 

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