Biotech Values

[mouton29]

<<I agree he was fumbling, but at the same time she wouldn't let up on it. It seems like he was trying to get to that main point, but she kept harping on whether MNTA's test is required for approval>>

Yes, and Amphastar's lawyer contended that their interpretation would not invalidate all process patents, only patents relating to a unique test required by the FDA. I'm not sure why that should matter, but on the question of whether the law in fact requires MNTA's test, the relevant provision seems to be

SEC. 501. [21 USC §351] Adulterated Drugs and Devices
A drug or device shall be deemed to be adulterated—
...


(b) If it purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength differs from, or its quality or purity falls below, the standards set forth in such compendium. Such determination as to strength, quality, or purity shall be made in accordance with the tests or methods of assay set forth in such compendium, except that whenever tests or methods of assay have not been prescribed in such compendium, or such tests or methods of assay as are prescribed are, in the judgment of the Secretary, insufficient for the making of such determination, the Secretary shall bring such fact to the attention of the appropriate body charged with the revision of such compendium, and if such body fails within a reasonable time to prescribe tests or methods of assay which, in the judgment of the Secretary, are sufficient for purposes of this paragraph, then the Secretary shall promulgate regulations prescribing appropriate tests or methods of assay in accordance with which such determination as to strength, quality, or purity shall be made. No drug defined in an official compendium shall be deemed to be adulterated under this paragraph because it differs from the standard of strength, quality, or purity therefor set forth in such compendium, if its difference in strength, quality, or purity from such standards is plainly stated on its label. Whenever a drug is recognized in both the United States Pharmacopeia and the Homeopathic Pharmacopeia of the United States it shall be subject to the requirements of the United States Pharmacopeia unless it is labeled and offered for sale as a homeopathic drug, in which case it shall be subject to the provisions of the Homeopathic Pharmacopeia of the United States and not to those of the United States Pharmacopeia.

http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCActChapterVDrugsandDevices/ucm108055.htm

Regulations interpreting this don't seem to require a unique test:

CPG Sec. 420.400 Performance of Tests for Compendial Requirements on Compendial Products


BACKGROUND:


There have been inquiries from the field and industry concerning the following four items as they apply to the manufacture of compendial (USP/NF) drug products.


1. Does a firm have to use the compendial methodology on a batch release basis, to determine whether its product meets the requirements of the monograph?


2. Does the word, "specifications" as used in 21 CFR 211.165 refer to compendial specifications or those set up by the firm's quality control unit?


3. Does a firm have to test for all requirements listed in the monograph for a compendial product?


4. Are the compendial testing requirements the same for products destined for the commercial market and the military?


POLICY:


1. Compendial methods need only be applied, as a batch release test, where a firm has made specific commitments to do so (as in a new drug application), or where the official method is the only appropriate test. It should be noted that neither the USP/NF nor the CGMP regulations necessarily require a firm to utilize, as a batch release test, the methods and procedures stated in the official compendia.


What is required is that official drug products conform to the appropriate compendial standards. This conformance must be assured by suitable means, including adequate manufacturing process validation and control. Scientifically sound alternative test methods may be acceptable for the purpose of batch release testing. However, in the event of a dispute as to whether or not a drug product meets the standard, the compendial method will be applied as the referee test.


2. The term "specifications" as used in 21 CFR 211.165 refers to the criteria established by manufacturers to assure that their products have the properties they purport to possess. Typically, these specifications are identical to, or more stringent than those contained in the compendia themselves. However, the manufacturer's specifications for standards of strength, quality and purity may be less stringent in those cases in which the differences from the official standards are stated on the product label; such alternate standards must not adversely affect the product's safety or efficacy.


3. Where an official product purports to conform to the standards of the USP/NF the manufacturer must assure that each batch conforms to each monograph requirement. This assurance must be achieved by appropriate means, including process validation and controls and end product testing. However, the nature and extent of end product testing which is needed will depend upon the circumstances. Factors to consider in determining the need to test each batch for a given monograph requirement include: the adequacy of the manufacturer's process validation, adequacy of in-process manufacturing controls, and the nature of the particular product characteristic which is the subject of the specification (e.g. potency, sterility, content uniformity). Therefore, in some cases it may not be necessary for a manufacturer to test each batch for each monograph requirement.



4. Compendial testing requirements are the same for products destined for commercial and military use unless the Defense Personnel Support Center (DPSC) insists upon certain requirements as part of military contracts. For example, DPSC can insist that only compendial methods be used and that each batch be tested for every monograph specification, whereas, as explained above, FDA considers that alternative procedures may sometimes be acceptable. Under the Government Wide Quality Assurance Program FDA must assure that the drug manufacturer abides by the terms of the military contract, including testing requirements.


Issued: 10/1/80

http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074370.htm

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