[Code of Federal Regulations]
[Title 21, Volume 7]
[Revised as of April 1, 2007]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR610.13]

[Page 73-74]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 610_GENERAL BIOLOGICAL PRODUCTS STANDARDS--Table of Contents
 
                      Subpart B_General Provisions
 
Sec.  610.13  Purity.

    Products shall be free of extraneous material except that which is 
unavoidable in the manufacturing process described in the approved 
biologics license application. In addition, products shall be tested as 
provided in paragraphs (a) and (b) of this section.
    (a)(1) Test for residual moisture. Each lot of dried product shall 
be tested for residual moisture and shall meet and not exceed 
established limits as specified by an approved method on file in the 
biologics license application. The test for residual moisture may be 
exempted by the Director, Center for Biologics Evaluation and Research 
or the Director, Center for Drug Evaluation and Research, when deemed 
not necessary for the continued safety, purity, and potency of the 
product.
    (2) Records. Appropriate records for residual moisture under 
paragraph (a)(1) of this section shall be prepared and maintained as 
required by the applicable provisions of Sec. Sec.  211.188 and 211.194 
of this chapter.
    (b) Test for pyrogenic substances. Each lot of final containers of 
any product intended for use by injection shall be

[[Page 74]]

tested for pyrogenic substances by intravenous injection into rabbits as 
provided in paragraphs (b) (1) and (2) of this section: Provided, That 
notwithstanding any other provision of Subchapter F of this chapter, the 
test for pyrogenic substances is not required for the following 
products: Products containing formed blood elements; Cryoprecipitate; 
Plasma; Source Plasma; Normal Horse Serum; bacterial, viral, and 
rickettsial vaccines and antigens; toxoids; toxins; allergenic extracts; 
venoms; diagnostic substances and trivalent organic arsenicals.
    (1) Test dose. The test dose for each rabbit shall be at least 3 
milliliters per kilogram of body weight of the rabbit and also shall be 
at least equivalent proportionately, on a body weight basis, to the 
maximum single human dose recommended, but need not exceed 10 
milliliters per kilogram of body weight of the rabbit, except that: (i) 
Regardless of the human dose recommended, the test dose per kilogram of 
body weight of each rabbit shall be at least 1 milliliter for immune 
globulins derived from human blood; (ii) for Streptokinase, the test 
dose shall be at least equivalent proportionately, on a body weight 
basis, to the maximum single human dose recommended.
    (2) Test procedure, results, and interpretation; standards to be 
met. The test for pyrogenic substances shall be performed according to 
the requirements specified in United States Pharmacopeia XX.
    (3) Retest. If the lot fails to meet the test requirements 
prescribed in paragraph (b)(2) of this section, the test may be repeated 
once using five other rabbits. The temperature rises recorded for all 
eight rabbits used in testing shall be included in determining whether 
the requirements are met. The lot meets the requirements for absence of 
pyrogens if not more than three of the eight rabbits show individual 
rises in temperature of 0.6 [deg]C or more, and if the sum of the eight 
individual maximum temperature rises does not exceed 3.7 [deg]C.

[38 FR 32056, Nov. 20, 1973, as amended at 40 FR 29710, July 15, 1975; 
41 FR 10429, Mar. 11, 1976; 41 FR 41424, Sept. 22, 1976; 44 FR 40289, 
July 10, 1979; 46 FR 62845, Dec. 29, 1981; 49 FR 15187, Apr. 18, 1984; 
50 FR 4134, Jan. 29, 1985; 55 FR 28381, July 11, 1990; 64 FR 56453, Oct. 
20, 1999; 67 FR 9587, Mar. 4, 2002; 70 FR 14985, Mar. 24, 2005]