Stand-alone protocols

Associated tests to include are leak rate and vacuum integrity tests. Both tests are based on the pressure rise of a sealed chamber and condenser that are isolated from the vacuum pumping system. A detailed presentation on the subject is covered in various technical publications on vacuum technology [3,4], Each of these tests, briefly described in the following paragraphs, is well suited to be stand-alone protocols. 

The 1999 guidance on Population Pharmacokinetics issued by the Food and Drug Administration (FDA) differentiates two types of DAPs, which they refer to as Study Protocols. The first type is an add-on DAP which is seamlessly interwoven into the clinical protocol from which the pharmacokinetic data will be derived. The other type is a stand-alone DAP, which is independent of any clinical protocols, and can standalone by itself without reference to other protocols. Stand-alone protocols are useful when data from many different studies will be analyzed. In the guidance issued by the ICH, it is suggested that the essential features of the analysis are included in the clinical protocol, but that the details of the analysis are identified in a stand-alone SAP. 

The LC control software, either stand-alone or as part of an overall data-handling system, should be tested by means of a separate OQ protocol. This protocol only needs to address the communica-tions/control integrity of the hardware (e.g., setting up a run/sequence with the proper instrument parameters, the ability to start and stop the pump, etc.). It should cover all the required instrument control functions listed as part of the protocol s functional specifications. It does not need to include specific hardware performance testing, such as linearity or flow rate. The latter tests are performed separately, as part of the individual hardware validation described below. 

This reaction has developed a number of related protocols and variations. Some have earned sufficient recognition to act as "stand alone" reactions and will be found under their own headings in this monograph. 

The statistical review may also take a more global view and, in addition to evaluating the aspects of each protocol in a stand-alone fashion, evaluate how it fits in with and adds to the overall drug development program. 

Figure 3.1.1-1 gives an example of a stand-alone 28-day TDAR protocol in rats. A 28-day study is recommended, although other study durations may be... 

Figure 3.1.1-1 Example of a stand-alone primary TDAR protocol in rats. Animals (8-10/sex/group) are treated with test compound (low, mid, and high doses) or vehicle by a clinically relevant route for 28 consecutive days. (A) Rats are given a single intravenous injection of KLH on Day 24, and serum collected on Day 29 for determination of IgM specific for KLH. (B) Alternatively, animals are immunized with KLH on Day 15, and serum collected on Days 20 and 29 for measurement of anti-KLH IgM and IgG, respectively.

Additional parameters that are readily incorporated into a stand-alone immune function test such as the KLH-TDAR model include ex vivo lymphocyte proliferation, cytokine protein expression, and immunophenotype analysis any or all of which can enhance hazard identification and characterization of a potential immunotoxicant. While the KLH-TDAR is an example of a combined immune function screen and mechanistic study, the ex vivo methodologies described herein are generally applicable to toxicology studies that do not include an immunization protocol. Moreover, the methodologies are not species-specific however, responsiveness to various stimulants to induce ex vivo lymphocyte proliferation and cytokine production may differ across species and strain, requiring procedural optimization for a given species and ex vivo test. 

Petersen, M., 2008, The legality of the EU s stand-alone approach to the climate impact of aviation the express role given to the ICAO by the Kyoto protocol. Review of European Community and International Environmental Law 17(2), 196-204. 

The system can be operated from stand-alone control via an LCD and a membrane keypad screen on the instrument. Seven pre-programmed protocols are provided and a maximum of 36 sequences containing 101 amino acids in length in each of the eight user profiles is allowed. Alternatively, for more flexibility, full protocol editing, chemical editing, and database capability, the system can be controlled from a computer workstation with icon-driven easy-to-use Windows 95-based software. 

Field Emission Gun with Energy Dispersive X-ray detection (FEG/EDX) interfaced with MRS is illustrated in Fig. 8, where it is observed that the particle has undergone changes after exposure to the electron beam. In addition, Raman spectra obtained after exposure to the electron beam showed band broadening, higher background and lower spectral quality. To this end, the importance of a robust protocol to be used for the analysis of environmental particles (especially of the finer fraction) with an interfaced two tier approach has been illustrated. It also seems from these preliminary observations that the protocol may have to be particle type specific. In addition, particle behaviour when exposed to the interfaced instrument may not mirror its behaviour when analysed under stand-alone conditions. 

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