Regulatory acceptance

Q4B Regulatory Acceptance of Analytical Procedures and/or Acceptance Criteria (RAAPAC) Quality of Biotechnological Products... 

Jaworska, J.S., Bomber, M., Auer, C. and Van Leeuwen, C.J. (2003). Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints. Environmental Health Perspective 111 1358-1360. 

Evaluate hydrogeologic conditions Requires regulatory acceptance Site specific... 

J. H. Fentem and P. A. Botham. Update on the validation and regulatory acceptance of alternative tests for skin corrosion and irritation. Altem. Lab. Anim. 32 683-688 (2004). 

Volpe DA, Moller H, Yu LX (2002) Regulatory acceptance of in vitro permeability studies in the context of the biopharmaceutics classification system. In Lehr CM (ed.) Cell Culture Models of Biological Barriers In Vitro Test Systems for Drug Absorption and Delivery. Taylor Francis Publishing Group, London New York, pp. 130-139. 

The FDA maintains a database of approved excipients Drug Information Electronic Orange Book, http //www.fda.gov/cder/ob/default.htm). Standards and tests for regulatory acceptable excipients are included in the US Pharmacopoeia and National Formulary. Two such tests, dissolution and stability, are included in Exhibit 5.12 for reference. For new excipients to be included in a drug formulation, they have to satisfy one of the following criteria ... 

Currently, there are no validated and regulatory accepted in vitro methods for assessing acute toxicity. 

Currently, there are no validated and regulatory accepted in vitro methods for assessing repeated dose toxicity. Numerous in vitro systems have been developed over the last decades and have been discussed and summarized in recent ECVAM reports on repeated dose toxicity testing (Worth and Balls 2002, Prieto et al. 2005, Prieto et al. 2006). Human in vitro data, particularly on kinetics and metabolism, and in vitro test data from well-characterized target organ and target system models on, e.g., mode of action(s)/mechanism(s) of toxicity may be useful in the interpretation of observed repeated dose toxicity. 

Several in vitro methods, including the hen s egg chorioallantoic membrane test (HET-CAM) the bovine cornea opacity and permeability assay (BCOP) and the isolated rabbit eye (IRE) test, have gained regulatory acceptance in Europe for the classification of severe eye irritants. Many companies are using such techniques successfully to reduce in vivo testing during development. ... 

Unfortunately, up to now none of these assays has received regulatory acceptance. 

At the 17th meeting of the ECVAM Scientific Advisory Committee in 2001, the EST, the MM assay, and the WEC assay were endorsed as scientifically validated assays and ready for consideration for regulatory acceptance. Detailed reports on the performance of these validated assays have been published (5-7). 

In 2007, the DART committee held a workshop on alternative assays, which was followed up by a workshop held at the European Teratology Society Annual Meeting in 2009. These workshops focused on three alternative assays (1) whole embryo culture (WEC), (2) mouse embryonic stem cell tests (mESC), and (3) zebrafish. Each assay was presented and data from users were shared, and strengths and limitations were discussed. It should be noted that the WEC and mESC are validated by ECVAM as alternative embryotoxicity assays. Still, there are numerous research needs before even validated tests can achieve regulatory acceptance. The discussions, conclusions, and recommendations of the 2007 workshop were published by Chapin et al. (14). Bullet lists of next steps to move forward were defined for each assay (14) and are briefly summarized here ... 

Once the test method has been validated, the ECVAM Scientific Advisory Committee (ESAC) produces a statement or recommendation on the use of the test method. In some cases, regulatory acceptance is achieved via adoption of the test method by a relevant European commission (e.g., a new Commission Regulation) or a new OECD Test Guideline (Organisation for Economic Co-operation and Development (OECD)). 

KoCVAM was announced in 2009 and established in 2010. In March 2011, KoCVAM joined the 2009 agreement known as the International Cooperation on Alternative Test Methods (ICATM) that had previously been formed with Europe, Canada, the USA, and Japan (33). This agreement will promote international cooperation on the validation of new test methods. It is envisioned that this cooperative effort will result in the most vigorous and robust science, thereby promoting regulatory acceptance. 

The requirements of 21 CFR Part 11 apply well beyond the laboratory environment, but do stand as supplemental to and interpretative of the GLP in automated laboratory environments. Comphance requires an understanding of the key elements of the Part 11 document, and the formulation of a strategy that assures safety, regulatory acceptance, and cost-effective management. 

As a result, vahdation represents a prudent, cost-effective, and efficient way of assuring regulatory acceptance as well as internal control of automated laboratories and the system upon which they rely. 

Because of the expense and effort of a comprehensive vahdation this review may be very cost-effective. The reclassification of a single system from group A to group B may result in saving 50,000 or more without compromising product or process safety, quahty, or regulatory acceptance. 

While this recommendation wiU have a longterm effect of discouraging innovation, it nonetheless will meet the goal of minimizing validation effort without compromise of quality or regulatory acceptance. All things being equal, select software that is prevalidated or in wide use. 

The use of an effective and category-hmiting change and maintenance procedure can lower the frequency of revalidation and can ease the process when re validation is required. In both situations, significant cost savings can be realized with loss of quality control or regulatory acceptance. 

For meta-analyses where these requirements are not fulfilled it will prove difficult to get a regulatory acceptance ... 

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