Compendial standard

One of the greatest tasks in providing compendial standards is to obtain, adapt, or develop test methods for determining compliance with the standards. Such methods must be capable of routine use in many laboratories by different personnel and equipment. There is a vast difference between a method that can be used in one laboratory by speciaHsts and one that can be used in many laboratories by generaHsts to determine whether chemicals pass or fail the estabHshed specifications. Additionally, the deterrninations must be reHable, because the results obtained may determine whether a product is safe or legal. 

A number of alternative sizing methods are available, and these are described in Table 8. The American Association of Pharmaceutical Scientists, Inhalation Focus Group conducted a comprehensive review of available methods, which was published in a series of articles identified in the last column of the table. All of the methods described either have been or are currently employed in the development of aerosol products. However, at this time only the inertial samplers, cascade impactors and impingers appear in compendial standards and in regulatory guidelines [44-46], Other methods such as thermal imaging are also under development and may give complementary size information to the current methods. 

A proposal to merely publish the official standards, allowing any apparatus to be used in regulatory filing to meet the standard, met with opposition by the USP (11). Clearly, the compendial standard required a specific procedure to allow the demonstration of compliance. 

The need to develop compendial standards for dissolution for capsules and tablets containing poorly soluble drug products was noted by the BP in 1973. By 1980, the British Pharmacopoeia Commission had identified a list of drug products included in the 1973 BP for which the development of a dissolution standard was necessary. The list included products... 

Where the specific impnrity is unavailable or is too costly, the use of composite or degraded samples is possible. This approach involves the nse of a dirty sample of a drug substance or the creation of a mixture of impurities through the in situ forced degradation method. Both of these approaches are best nsed for qualitative uses. In each of these mixtures, the impurities are present in unknown quantities. The real benefit of this type of impnrity standard is the low cost and the ability to unequivocally identify the peak loci of the impurities. When these mixtures are used in conjunction with a compendial standard and a well-developed set of relative response factors the resnlts will meet most analytical needs. 

Fig. 3 is designed to help illustrate which compendial standards are applicable to each packaging circumstance. 

Fig. 3 This decision tree should help identify those USP compendial standards that apply to a given new package design.

It is undoubtedly impossible to achieve harmonization of quality for new drugs without harmonization of compendial standards and methodology. The PDG will continue to proceed with what it believes to be the correct approach to pharmacopeial harmonization and to contribute to advancing effective harmonization for the quality of new drugs and products. 

In this manner, key objectives of harmonization will be attained only when the PDG is able to achieve mutually agreeable standards and test methods, which provide the same conclusions when performed on the same specimens, even if they use different specifications, procedures, or reagents. We should continue to take necessary steps to deepen international cooperation and to obtain harmonized compendial standards and methodology, using the PDG as the forum for harmonization of drug quality. 

Essential aspects of compendial standards are intrinsic in the history and composition of the Convention. USP standards are meant to describe an acceptable article from the point of view of the physician-pharmacist-patient interfaces and they are inherently time-of-use (that is, shelf life) requirements. Another outcome of this focus is that practical, medically significant aspects are dominant in assigning requirements and the limits therein. Compendial standards are always established from the viewpoints of the medical and pharmaceutical professions, which in the United States are represented by the USPC. 

As noted previously, compendial standards arose from the professions on behalf of the public. There are no attempts at regulation by the USP of the daily application of pharmaceutical technology. USP standards are not to be confused with such concepts as the product description. As addressed below, compendial standards are not manufacturing directions as such and do not constitute the manufacturers release criteria. They define the acceptable article as and when used. 

Why do we persist in saying public standards Because compendial standards, proposed and adopted, are published and circulated in public. The standards state to the public, manufacturers, and professions what constitutes predictable drug product quality from lot to lot and from manufacturer to manufacturer. 

We accept the inevitability of imperfection, thus we must accept the inevitable need for quality standards. Thus must we also accept the imperfection of those same quality standards. Compendial standards must be what can be done failure to publish a standard because it is imperfect can be failure to serve the public. I submit that a willingness to move forward in the face of imperfections is consistent with the second maxim stated by Descartes, which applies to any uncertain situation, to move resolutely and unswervingly in the most promising direction. 

Confusion of compendial standards with release tests and with statistical sampling plans occasionally occurs. Interpretation of results from official tests and assays requires an understanding of the nature and style of compendial standards. Tests and assays given in the USP prescribe operation on a single specimen that is, the singlet determination. This is the minimum... 

The advance of pharmaceutical technology ever forces forward new or refined excipients, some with heretofore unexploited properties. Polymers are a case in point and have been central to many of the technological advances of recent years. New and different challenges for compendial standards are offered by materials used in new wave formulations. Modern analytical chemistry allows rather thorough evaluation of materials. 

There are national pharmacopeias established by governments to meet perceived needs for compendial standards for locally produced articles. A number of these have published recent editions as evidence of continuing commitment, but it is often difficult to locate a U.S. bookseller for these. Cities of publication are Berlin, Paris, Prague, Rome, Tokyo, Peking, Seoul, Stuttgart, and Taipei. Most countries require imported articles to conform to one or another widely recognized pharmacopeia, such as the USP or the British Pharmacopeia. 

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