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(d) Requests for certification; samples. (1) In addition to complying with the requirements of $ 146.2, a person who requests certification of a batch of penicillin bougies shall submit with his request a statement showing the batch mark, the number of packages of each size in such batch, the batch mark and (unless it was previously submitted) the date on which the latest assay of the penicillin used in making such batch was completed, the number of units in each bougie, the quantity of each ingredient used in making the batch, and the date on which the latest assay of the drug comprising such batch was completed.

(2) Except as otherwise provided by subparagraph (4) of this paragraph such person shall submit in connection with his request results of the tests and assays listed after each of the following, made by him on an accurately representative sample of:

(i) The batch; average potency per bougie, moisture, microorganism count.

(ii) The penicillin used in making the batch; potency, toxicity, moisture, pH, crystallinity, and heat stability if it is crystalline penicillin, and the penicillin G content if it is crystalline penicillin G.

(3) Except as otherwise provided by subparagraph (4) of this paragraph such person shall submit in connection with his request in the quantities hereinafter indicated, accurately representative samples of the following:

(i) The batch; one bougie for each 5,000 bougies in the batch, but in no case less than bougies or more than 100 bougies, collected by taking single bougies at such intervals throughout the entire time the bougies are being made, that the quantities made during the intervals are approximately equal.

(ii) The penicillin used in making the batch; five packages, or in the case of crystalline penicillin 10 packages, each containing approximately equal portions of not less than 60 milligrams each, packaged in accordance with the requirements of $ 146.24 (b).

(iii) In case of an initial request for certification, one package of each polyethylene glycol used in making the batch, each containing approximately 25 grams.

(4) No result referred to in subparagraph (2) (ii) of this paragraph, and no sample referred to in subparagraph (3) (ii) of this paragraph, is required if such

result or sample has been previously submitted.

(e) Fees. The fee for the services rendered with respect to each batch of penicillin bougies under the regulations in this part shall be:

(1) $2.00 for each bougie in the sample submitted in accordance with paragraph (d) (3) (i) of this section; $4.00 for each package in the samples submitted in accordance with paragraph (d) (3) (ii) and (iii) of this section; and

(2) If the Commissioner considers that investigations other than examination of such bougies and packages, are necessary to determine whether or not such batch complies with the requirements of $ 146.3 for the issuance of a certificate, the cost of such investigations.

The fee prescribed by subparagraph (1) of this paragraph shall accompany the request for certification unless such fee is covered by an advance deposit maintained in accordance with $ 146.8 (d). [Reg., July 21, 1947, effective July 25, 1947, 12 F.R. 4962, 5039)

$ 146.41 Crystalline penicillin and epinephrine in oil-(a) Standards of identity, strength, quality, and purity. Crystalline penicillin and epinephrine in oil is a suspension of crystalline penicillin and epinephrine in a menstruum of refined peanut oil or sesame oil. Each milliliter has a potency of 300,000 units and contains 0.3 milligram of epinephrine. Its moisture content is not more than 0.2 percent. It is sterile. The penicillin used conforms to the requirements of $ 146.24 (a) for crystalline penicillin except subparagraph (7) of $ 146.24 (a). The epinephrine, peanut oil and sesame oil used conform to the standards prescribed therefor by the U. S. P.

(b) Packaging. The immediate container of crystalline penicillin and epinephrine in oil shall be of colorless transparent glass so closed as to be a tight container as defined by the U.S. P., shall be sterile at the time of filling and closing, shall be so sealed that its contents cannot be used without destroying such seal, and shall be of such composition as will not cause any change in the strength, quality, or purity of the contents beyond any limit therefor in applicable standards, except that minor changes SO caused which are normal and unavoidable in good packaging, storage, and distribution practice shall be disregarded. The quality of crystalline penicillin and

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epinephrine in oil in each such container shall be not less than one milliliter and not more than 20 milliliters unless it is packaged for repacking. Unless it is packaged for repacking each container shall be filled with a volume of crystalline penicillin and epinephrine in oil in excess of that designated, which excess shall be sufficient to permit the withdrawal and the administration of the volume indicated whether administered in either single or multiple doses.

(c) Labeling. Each package of crystalline penicillin and epinephrine in oil shall bear, on its label or labeling as hereinafter indicated, the following:

(1) On the outside wrapper or container and the immediate container of the package:

(i) The batch mark;

(ii) The number of units per milliliter of the batch;

(iii) The quantity of epinephrine per milliliter of the batch; (iv) The statement "Expiration date

the blank being filled in with the date which is 18 months after the month during which the batch was certified; and

(v) The statements "For intramuscular use only" and "Shake Well”.

(2) On the circular or other labeling within or attached to the package, adequate directions for use and warnings as required by section 502 (f) of the act, including:

(i) Clinical indications:

(ii) Dosage and administration, including site of injection;

(iii) Contraindications; and

(iv) Untoward effects that may accompany administration, including sensitization.

(d) Requests for certification; samples. (1) In addition to complying with the requirements of $ 146.2, a person who requests certification of a batch of crystalline penicillin and epinephrine in oil shall submit with his request a statement showing the batch mark, the number of packages of each size in such batch, the batch mark and (unless it was previously submitted) the date on which the latest assay of the penicillin used in making such batch was completed, the number of units in each of such packages, the quantity of each ingredient used in making the batch, the date on which the latest assay of the drug comprising such

batch was completed, and that the epinephrine, peanut oil or sesame oil used in making such batch conforms to the requirements prescribed therefor by this section.

(2) Except as otherwise provided by subparagraph (4) of this paragraph, such person shall submit in connection with his request results of the tests and assays listed after each of the following, made by him on an accurately representative sample of:

(i) The batch; potency, sterility, moisture and epinephrine content;

(ii) The penicillin used in making the batch; potency, sterility, toxicity, pyrogens, moisture, pH, penicillin K content (unless it is crystalline penicillin G), crystallinity, heat stability and the penicillin G content if it is crystalline penicillin G.

(3) Except as otherwise provided by subparagraph (4) of this paragraph, such person shall submit in connection with his request, in the quantities hereinafter indicated, accurately representative samples of the following:

(i) The batch; one package for each 500 packages in the batch, but in no case less than 5 packages or more than 15 packages, collected by taking single packages at such intervals throughout the entire time of packaging the batch that the quantities packaged during the intervals are approximately equal.

(ii) The penicillin used in making the batch; ten packages containing approximately equal portions of not less than 60 milligrams each, packaged in accordance with the requirements of g 146.24 (b).

(iii) In case of an initial request for certification, the epinephrine and the peanut oil or sesame oil used in making the batch; one package of each containing approximately 2 grams and 250 grams respectively.

(4) No result referred to in subparagraph (2) (ii) of this paragraph, and no sample referred to in subparagraph (3) (ii) of this paragraph, is required if such result or sample has been previously submitted.

(e) Fees. The fee for the services rendered with respect to each batch of crystalline penicillin and epinephrine in oil under the regulations in this part shall be:

(1) $8.00 for each immediate container submitted in accordance with paragraph (d) (3) (i), $4.00 for each package in the

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samples submitted in accordance with paragraph (d) (3) (ii) and (iii) of this section; and

(2) If the Commissioner considers that investigations, other than examinations of such packages, are necessary to determine whether or not such batch complies with the requirements of § 146.3 for the issuance of a certificate, the cost of such investigation.

The fees prescribed by subparagraph (1) of this paragraph shall accompany the request for certification unless such fee is covered by an advance deposit maintained in accordance with $ 146.8 (d). (Reg., Nov. 29, 1947, effective Dec. 5, 1947, 12 F.R. 8152]

$ 146.101 Streptomycin sulfate, streptomycin hydrochloride, streptomycin phosphate, streptomycin trihydrochloride calcium chloride-(a) Standards of identity, strength, quality, and purity. Streptomycin sulfate is the sulfate salt of a kind of streptomycin or a mixture of two or more such salts; streptomycin hydrochloride is the hydrochloride salt of a kind of streptomycin or a mixture of two or more such salts; streptomycin phosphate is the phosphate salt of a kind of streptomycin or a mixture of two or more such salts; streptomycin trihydrochloride calcium chloride is the double salt of a kind of streptomycin or a mixture of two or more such salts. Each such drug is so purified and dried that:

(1) Its potency is not less than 300 micrograms per milligram;

(2) It is sterile;
(3) It is nontoxic;
(4) It is nonpyrogenic;

(5) It contains no histamine or histamine-like substances;

(6) Its moisture content is not more than 3.0 percent;

(7) Its pH in aqueous solution of 0.2 gram per millimeter is not less than 4.5 and not more than 7.0;

(8) Its solution in water for injection U.S.P., dextrose injection 5.0 percent U.S. P., or physiological salt solution U.S.P., prepared by adding 0.2 gram (estimated) of streptomycin per milliliter, is of such clarity that it is substantially free of any turbidity or undissolved material.

(b) Packaging. In all cases the immediate container shall be a tight container as defined by the U. S. P., shall be sterile at the time of filling and clos

ing, shall be so sealed that the contents cannot be used without destroying the seal, and shall be of such composition as will not cause any change in the strength, quality, or purity of the contents beyond any limit therefor in applicable standards, except that minor changes so caused which are normal and unavoidable in good packaging, storage, and distribution practice shall be disregarded. In case it is packaged for dispensing it shall be in immediate containers of colorless transparent glass which meet the test for glass containers of type I or type II prescribed by the U. S. P., closed by a substance through which a hypodermic needle may be introduced and withdrawn without removing the closure or destroying its effectiveness; each such container shall contain 0.5 gram, 1.0 gram, 2.0 grams, 3.0 grams, 4.0 grams, 5.0 grams, or 10.0 grams, and each may be packaged in combination with a container of the solvent, water for injection U. S. P., dextrose injection 5 percent U. S. P., or physiological salt solution U. S. P.

CODIFICATION: In the second sentence of $ 146.101 (b), the word "or" preceding the words "5.0 grams" was deleted, and the words "or 10.0 grams" were inserted following the words "5.0 grams", by Regulation, Administrator, Sept. 10, 1947, 12 F.R. 6109, 6401.

(c) Labeling. Each package shall bear on its label or labeling as hereinafter indicated, the following:

(1) On the outside wrapper or container and the immediate container:

(i) The batch mark;

(ii) The number of grams in the immediate container; (iii) The statement "Expiration date

--", the blank being filled in with the date which is 12 months after the month during which the batch was certified; and

(iv) The statement "For Manufacturing Use", "For Repacking", or "For Manufacturing Use or Repacking" when

ged for repacking or for use as an ingredient in the manufacture of another drug, as the case may be.

(2) On the circular or other labeling within or attached to the package, if it is packaged for dispensing, adequate directions for use and warnings as required by section 502 (f) of the act, including:

(1) Clinical indications;

(ii) Dosage and administration, including method of preparation and strength of solutions for different routes of injection and local application;

(iii) The conditions under which such solutions should be stored including the statement “Sterile solution may be stored at room temperature for one week without significant loss of potency";

(iv) Contraindications; and

(v) Untoward effects that may accompany administration, including sensitization.

If two or more immediate containers are in such package, the number of such circulars or other labeling shall not be less than the number of such containers.

(d) Requests for certification, check tests, and assays; samples. (1) In addition to complying with the requirements of $ 146.2, a person who requests certification of a batch shall submit with his request a statement showing the batch mark, the number of packages of each size in the batch, the number of grams in each package, and (unless it was previously submitted) the date on which the latest assay of the drug comprising the batch was completed. Such request shall be accompanied or followed by the results of tests and assays made by him on the batch for potency, sterility, toxicity, pyrogens, histamine content, moisture, pH, and clarity. If such batch or any part thereof is to be packaged with a solvent such request shall also be accompanied by a statement that such solvent conforms to the requirements prescribed therefor by this section.

(2) If such batch is packaged for dispensing, such person shall submit with his request a sample consisting of one immediate container for each 5,000 immediate containers in such batch, but in no case shall such sample consist of less than 5 or more than 12 immediate containers.

Such sample shall be collected by taking single immediate containers, before or after labeling, at such intervals throughout the entire time of packaging the batch that the quantities packaged during the intervals are approximately equal.

(3) If such batch is packaged for repacking or for use as an ingredient in the manufacture of another drug, such person shall submit with his request a sample containing five approximately equal

portions of at least 0.5 gram each taken from different parts of such batch; each such portion shall be packaged in a separate container, and in accordance with the requirements of paragraph (b) of this section.

(4) In connection with contemplated requests for certification of repackaged batches or batches of another drug in the manufacture of which it is to be used, the manufacturer of a batch which is to be so repacked or used may request the Commissioner to make check tests and assays on a sample of such batch taken as prescribed by subparagraph (3) of this paragraph. From the information required by subparagraph (1) of this paragraph may be omitted results of tests and assays not required for the batch when used in such other drug. The Commissioner shall report to such manufacturer results of such check tests and assays as are so requested.

(e) Fees. The fee for the services rendered with respect to each batch under the regulations in this part shall be:

(1) $15.00 for each immediate container in the sample submitted in accordance with paragraphs (d) (2), (3), and (4) of this section.

(2) If the Commissioner considers that investigations, other than examination of such immediate containers, are necessary to determine whether or not such batch complies with the requirements of $ 146.3 for the issuance of a certificate, the cost of such investigations.

The fee prescribed by subparagraph (1) of this paragraph shall accompany the request for certification unless such fee is covered by an advance deposit maintained in accordance with § 146.8 (d).

PART 155_SEA FOOD INSPECTION

CANNED SHRIMP Sec. 155.0 Application for inspection service.

(Amended) 155.1 Granting or refusing inspection

service; cancellation of applica

tion. (Amended] 155.2 Inspection periods. (Amended) 155.12 Inspection fees. (Amended)

CANNED OYSTERS

155.30 Application for inspection service.

(Amended]

Sec.
155.31 Granting or refusing inspection

service; cancellation of applica

tion. (Amended] 155.32 Inspection periods. (Amended] 155.42 Inspection fees. (Amended)

CANNED SHRIMP

$ 155.0 Application for inspection service.

CODIFICATION: In $ 155.0 (a), "8450" was changed to "$600", May 20, 1947, effective May 23, 1947, applicable only to service rendered on or after July 1, 1947, 12 F.R. 3318.

§ 155.1 Granting or refusing inspection service; cancellation of application.

(c) The applicant, by giving written notice to the Administrator, may withdraw his application for inspection seryice before July 1 preceding the inspection period covered by the application. In case of such withdrawal, the Administrator shall return to such applicant the payment which accompanied the application, less any salary and other expense incurred by the Administration incident to such application. (Paragraph (c) amended May 20, 1947, effective May 23, 1947, 12 F.R. 3318]

§ 155.2 Inspection periods.

CODIFICATION: In § 155.2 (a), "$300" was changed to "$500", May 20, 1947, effective May 23, 1947, applicable only to service to be rendered on or after July 1, 1947, 12 F.R. 3318.

$ 155.12 Inspection fees. (a) Except as otherwise provided by the regulations in this part, the fee prescribed for inspection service shall be fifteen (15) cents for each case of canned shrimp packed under such service in excess of the first 1,000 cases. For the purpose of this section a case of canned shrimp shall be 48 No. 1 cans (211 x 400) or the equivalent thereof. Advance deposits of not less than $300 shall be made whenever necessary to prevent arrears in the payment of fees, unless the Administration on an estimate of output authorizes payment in other amounts. Any excess advance deposits so made for the fiscal year shall be returned to the packer by the Administration after the inspection service is closed in the establishment. [Paragraph (a) amended May 20, 1947, effective May 23, 1947, 12 F.R. 3318]

(b) In addition to the fee prescribed by paragraph (a) of this section, as amended, an initial advance deposit of $600 (which includes a minimum case fee

of $200 for inspection service for the
first 1000 cases of canned shrimp packed
under the regulations in this part) shall
accompany each application for an ini.
tial inspection period; thereafter, seven
advance monthly deposits of $600 each
shall be made on or before the first day
of each month commencing July 1 and
continuing through January 1. When-
ever it is determined, without hearing,
by the Commissioner of Food and Drugs
that an establishment having the in-
spection service has been damaged by
wind, fire, flood, or other calamity, to
such an extent that packing operations
cannot be resumed before the end of
the fiscal year then current, no ad-
vance monthly deposits falling due after
such calamity will be required from the
operator of such establishment for that
fiscal year; but whenever it is deter-
mined, without hearing, by the Com-
missioner of Food and Drugs that an
establishment having the inspection
service has been so damaged by any
such calamity that packing operations
must be suspended temporarily, and
can be resumed before the end of the
fiscal year then current, payment of
the advance monthly deposits falling due
after such calamity and before the
month of resumption of operations shall
be postponed until operations are re-
sumed and thereupon shall be paid in
equal monthly installments during the
period between the time of resumption
of operations and June 1 of the fiscal
year then current: Provided, That in
the event of a determination described
in this sentence the total deposits made
by the operator involved shall be charged
with the cost of the service made avail-
able for the establishment, without re-
gard to the method provided hereinafter
for computing charges against deposits
and the balance of the total deposits
remaining after such charges shall be
returned by the Administration to the
operator of the establishment after the
completion of the fiscal year. Each
application for an extension inspection
period shall be accompanied by a de-
posit of $500, and at subsequent monthly
intervals thereafter additional deposits
of $500 shall be made; but if the final
deposit is to cover a time of less than 30
days, then such deposit shall be at the
rate of $16.67 for each day of such time.
Advance deposits made under this para-
graph shall be charged with the cost of
the inspection service which has not

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