Regulatory considerations

The FDA perspective is summarized in the following list to give the reader a bird s-eye view of what is likely to be required by various regulatory agencies for the stereochemistry of NCEs that have one or more chiral centers.  

The enantiomeric ratio should be defined for any admixture other than 50 50. 

Absolute configuration is desirable for an optically pure drug. Marketing an optical isomer requires a new NDA. 

Justification of the racemate or any of the optically active forms must be made with the appropriate data. 

Stress study data for drug substance Data from accelerated and long-term studies 

Pre-market submissions often concern the use of a food contact article that may be composed of a base polymer used in conjunction with several adjuvants, such as fillers, antioxidants, processing aids, or blended with other polymers. It is important to understand what previous regulatory authorizations can be relied upon, when anew submission is required, and when multiple submissions are necessary. 

For FCNs, specifications serve to ensure that the substance marketed by the manufacturer/supplier identified in the notification is the same as that subjected to the safety evaluation when the FCN became effective. Several specifications may be given in an FCN. Specifications are applicable only to the manufacturer/supplier identified in the FCN and are well known to them. Thus, they are generally not included in FCN letters. As noted above, the notifier is held to the specifications and use conditions identified in the FCN. Accordingly, changes in the manufacturing process that result in new impurity profiles may require communication with the FDA and, if warranted, new FCN submissions. 

Emissions from individual sources can be closely regulated, both within a facility (occupational standards) and outside it (with New Source Performance Standards at the federal level and/or Air Toxic Hot Spots regulations in California). The National Institute of Occupational Safety and Health (NIOSH) began in 1970, with the passage of the Occupational Safety and Health Act, to develop recommended exposure limits (RELs) for chemicals in the workplace. In 1974, NIOSH joined with OSHA to update the OSHA program for PELs for a wide variety of substances, incorporating cancer potency data as it became available over subsequent years. Their evaluations were published in criteria documents. Special Hazard Reviews, and summarized in a Compendium of Policy Documents and Statements (NIOSH 1992). Available information is periodically updated in the NIOSH Pocket 

The production of therapeutic antibodies is guided by the same principles as are applied for recombinant proteins or plasma proteins. A common rule is to check for potency, consistency, and purity at each level of the production 

Country Authority Field of regulation Internet address 

United States Center for Biologic Evaluation and Research (CBER) Releases points to consider for manufacturing of monoclonal antibodies and other biologies including test guidelines www.fda.gov/cber/points.htm 

Europe European Agency for the Regulatory authority of the European Commission www.eudra.org / en home.htm 

International International Conference on Releases guidelines for quality control, safety testing, www.pharmweb.nt/pwmirror / 

For the production of clinical-grade proteins, plant cell cultures and all downstream processing operations need to meet the standards that have been set for other 

The use of plant suspension cells for the production of biopharmaceutical proteins has many advantages, including safety, defined growth conditions, containment, and the ability to use continuous-culture strategies. However, some challenges remain to 

1 Doran PM (2000) Foreign protein production in plant tissue cultures. Curr Opin Biotechnol 11 199-204. 

2 Hellwig S, Drossard ), Twyman RM, Fischer R (2004) Plant cell cultures for the production of recombinant diagnostic and therapeutic proteins. Nature Biotechnol 22 1415-1422. 

3 Gomord V, Faye L (2004) Posttranslational modification of therapeutic proteins in plants. Curr Opin Plant Biol 7 171-181. 

For operational qualification of microwave components, such as forward and reflected power, and arc detection, we suggest that customers contact the vendors because of the specialized nature of microwave systems. The cost associated with the calibration equipment is difficult to justify, and microwave systems should operate reliably following proper setup and qualification and require no more periodic maintenance than other granulation approaches. 

When microwave processors were first introduced, there was the expectation that E-lield would be a reliable indicator of the drying end point. With experience, users found that the E-lield tends to be too variable, and now view it primarily as a safety feature monitoring the microwave field within the drying cavity. Most microwave driers on the market today do not even include E-field monitoring any more, because of the difficulties with validation of this system. 

Product temperature, time, cumulative forward power, and reflected power are proving to be more reliable indicators of drying end point with verification by some 

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Regulatory considerations, covering national and international standards with proposed future changes and developments... 

Asano T, Cotruvo JA (2004) Groundwater recharge with reclaimed municipal wastewater health and regulatory considerations. Water Res 38(8) 1941-1951... 

Regulatory considerations for residue analysis and methods on crops and food the approach of Japan... 

Regulatory considerations for environmental analytical methods for environmental fate and water quality impact assessments of agrochemicals... 

Shankar, G., Shores, E., Wagner, C., and Mire-Sluis, A. 2006. Scientific and regulatory considerations on the immunogenicity of biologies. Trends in Biotechnology 24, 274-280. 

Hastings, K.L. (2001) Pre-clinical methods for detecting the hypersensitivity potential of pharmaceuticals Regulatory considerations. Toxicology, 158, 85, 2001. 

SUPPLYING MATERIALS TO THE MEDICAL DEVICES INDUSTRY - REGULATORY CONSIDERATIONS... 

Vicenza, Italy, 18th Oct. 1996, p.17-24. 16 THE FUTURE OF DOP UNDER TECHNICAL, DEMOGRAPHIC AND REGULATORY CONSIDERATIONS... 

Scheuplein, R.J., Shoal, S.E., and Brown, R.N. (1990). Role of pharmacokinetics in safety evaluation and regulatory considerations. Ann. Rev. Pharamcol. Toxicol. 30 197-218. Smith, Charles G. (1992). The Process of New Drug Discovery and Development. CRC Press, Boca Raton, FL. 

The following subsections provide details concerning status, market approval authority, special label/regulatory considerations, investigational options, and inter-... 

Special label/regulatory considerations The following specific procedures will apply depending on the status of the drug delivery device and drugs that will be delivered with the device. 

Special label/regulatory considerations These products have a drug component that is present to augment the safety and/or efficacy of the device. 

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