Sec.

PART 200-GENERAL

Subpart A-General Provisions

200.5 Mailing of important information about drugs.

200.7 Supplying pharmacists with indications and dosage information. 200.10 Contract facilities (including consulting laboratories) utilized as extramural facilities by pharmaceutical manufactur

ers.

200.11 Use of octadecylamine in steam lines of drug establishments. 200.15

Definition of term "insulin."

Subpart B-Manufacturing Procedures
Affecting New Drug Status

200.30 Sterilization of drugs by irradiation. 200.31 Timed release dosage forms.

Subpart C-Requirements for Specific
Classes of Drugs

200.50 Ophthalmic preparations and dispensers.

Subpart D [Reserved]

Subpart E-Prescription Drug Consumer Price Listing

200.200 Prescription drugs; reminder advertisements and reminder labeling to provide price information to consumers. AUTHORITY: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 508, 515, 701, 704, 705 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351. 352, 353, 355, 356, 357, 358, 360e, 371, 374, 375).

SOURCE: 40 FR 13996, Mar. 27, 1975, unless otherwise noted.

Subpart A-General Provisions

§ 200.5 Mailing of important information about drugs.

Manufacturers and distributors of drugs and the Food and Drug Administration occasionally are required to mail important information about drugs to physicians and others responsible for patient care. In the public interest, such mail should be distinctive in appearance 80 that it will be promptly recognized and read. The Food and Drug Administration will make such mailings in accordance with

the specifications set forth in this section. Manufacturers and distributors of drugs are asked to make such mailings as prescribed by this section and not to use the distinctive envelopes for ordinary mail.

(a) Use first class mail and No. 10 white envelopes.

(b) The name and address of the agency or the drug manufacturer or distributor is to appear in the upper left corner of the envelope.

(c) The following statements are to appear in the far left third of the envelope front, in the type and size indicated, centered in a rectangular space approximately 3 inches wide and 21⁄4 inches high with an approximately 8 inch-wide border in the color indicated: (1) When the information concerns a significant hazard to health, the statement:

IMPORTANT DRUG

WARNING

The statement shall be in three lines, all capitals, and centered. "Important" shall be in 36 point Gothic Bold type. "Drug" and "Warning" shall be in 36 point Gothic Condensed type. The rectangle's border and the statement therein shall be red.

(2) When the information concerns important changes in drug package labeling, the statement:

IMPORTANT

PRESCRIBING

INFORMATION

The statement shall be in three lines, all capitals, and centered. "Important" shall be in 36 point Gothic Bold type. "Prescribing" and "Information" shall be in 36 point Gothic Condensed type. The rectangle's border and the statement therein shall be blue.

(3) When the information concerns a correction of prescription drug advertising or labeling, the statement:

IMPORTANT

CORRECTION

OF DRUG

INFORMATION

The statement shall be in four lines, all capitals, and centered. "Important" shall be in 36 point Gothic Bold type. "Correction, "Of Drug," and "Information" shall be in 36 point Gothic Condensed type. The rectangle's border and the statement therein shall be brown.

§ 200.7 Supplying pharmacists with indications and dosage information. There are presently no regulations under the Federal Food, Drug, and Cosmetic Act that prevent a manufacturer of prescription drugs from sending the pharmacist data he needs on indications and dosage in exercising his important professional function of checking against possible mistakes in a prescription. The Food and Drug Administration believes manufacturers should be encouraged to supply such printed matter to the pharmacist for his professional information. Obviously, such printed matter should not be displayed to prospective purchasers to promote over-the-counter sale of prescription

drugs.

§200.10 Contract facilities (including consulting laboratories) utilized as extramural facilities by pharmaceutical manufacturers.

(a) Section 704(a) of the Federal Food, Drug, and Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory, warehouse, or establishment in which prescription drugs are manufactured, processed, packed, or held.

(b) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products utilize extramural independent contract facilities, such as testing laboratories, contract packers or labelers, and custom grinders, and regards extramural facilities as an extension of the manufacturer's own facility.

(c) The Food and Drug Administration reserves the right to disclose to the pharmaceutical manufacturer, or

to the applicant of a new drug application (NDA) or to the sponsor of an Investigational New Drug (IND) Application, any information obtained during the inspection of an extramural facility having a specific bearing on the compliance of the manufacturer's, applicant's, or sponsor's product with the Federal Food, Drug, and Cosmetic Act. The Food and Drug Administration's position is that by the acceptance of such contract work, the extramural facility authorizes such disclosures.

(d) The Food and Drug Administration does not consider results of validation studies of analytical and assay methods and control procedures to be trade secrets that may be withheld from the drug manufacturer by the contracted extramural facility.

[40 FR 13996, Mar. 27, 1975, as amended at 55 FR 11576, Mar. 29, 1990]

in

§ 200.11 Use of octadecylamine steam lines of drug establishments. The Food and Drug Administration will not object to the use of octadecylamine in steam lines where the steam may be used for autoclaving surgical instruments and gauze if the octadecylamine in the steam is not more than 2.4 parts per million.

$ 200.15 Definition of term "insulin." For the purposes of sections 502(k) and 506 of the act:

(a) The term insulin as used therein means the active principle of pancreas which affects the metabolism of carbohydrate in the animal body and which is of value in the treatment of diabetes mellitus.

(b) The following substances, when they are intended for use in the manufacture of insulin-containing drugs that will subsequently be submitted for certification, shall not be considered to be subject to certification as "drugs composed wholly or partly of insulin": (1) Pancreas glands; and

(2) Materials prepared from pancreas glands, such as "salt cake" and "isoelectric precipitate," which materials must be subjected to further purification in order to meet the standards of purity established by part 429 of this chapter.

Subpart B-Manufacturing Procedures Affecting New Drug Status

EFFECTIVE DATE NOTE: At 62 FR 12084, Mar. 14, 1997, subpart B was removed, effective Apr. 14, 1997.

§200.30 Sterilization of drugs by irradiation.

There is a current interest in the utilization of newly developed sources of radiation for the sterilization of drugs. Prior to the marketing of a drug sterilized by such means, it is necessary in the interest of protecting the public health to establish by adequate investigations that the irradiation treatment does not cause the drug to become unsafe or otherwise unsuitable for use. Accordingly, all drug products, including injections, ophthalmic solutions, surgical sutures, and surgical dressings sterilized by means of irradiation are regarded as new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act. An effective new-drug application pursuant to section 505 of the act is therefore a prerequisite to interstate shipment of such articles, except as provided by section 505(i).

§200.31 Timed release dosage forms.

(a) Many drugs are now being offered in dosage forms that are designed to release the active ingredients over a prolonged period. There is a possibility of unsafe overdosage if such products are improperly made and the active ingredients are released at one time or over too short a time interval. Any such dosage form that contains per dosage unit (for example, capsule or tablet), a quantity of active drug ingredients which is not generally recognized as safe for administration as a single dose under the conditions suggested in its labeling, is regarded as a new drug within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act.

(b) The fact that the labeling of this type of drug may claim delayed or prolonged release of all or some of the active ingredients does not affect the new-drug status of such articles. A new-drug application is required in any such case to demonstrate that the drug

is in fact safe because it is properly made and controlled to release the total dose at a safe rate. It should be noted particularly that such dosage forms are regarded as new drugs even when the total daily dosage recommended in the labeling is generally recognized as safe. For example, a capsule containing 50 milligrams of pyrilamine maleate and 15 milligrams of phenylephrine hydrochloride, offered for sale without prescription, is regarded as a new drug for which the distributor should have an effective newdrug application, even though the directions call for taking no more than two capsules daily. While the daily intake under such directions is within the range regarded as safe for use in self-medication, the single dose is too high for such use unless the release of the drug is sufficiently prolonged. It is obvious that, in filing a new-drug application for such an article, particular attention should be given to data which establish that the active ingredients are released over a period of time, as represented in the labeling.

(a)(1) Informed medical opinion is in agreement that all preparations offered or intended for ophthalmic use, including preparations for cleansing the eyes, should be sterile. It is further evident that such preparations purport to be of such purity and quality as to be suitable for safe use in the eye.

(2) The Food and Drug Administration concludes that all such preparations, if they are not sterile, fall below their professed standard of purity or quality and may be unsafe. In a statement of policy issued on September 1, 1964, the Food and Drug Administration ruled that liquid preparations offered or intended for ophthalmic use that are not sterile may be regarded as adulterated within the meaning of section 501(c) of the Federal Food, Drug, and Cosmetic Act (the act), and, further, may be deemed misbranded within the meaning of section 502(j) of the act. This ruling is extended to affect all preparations for ophthalmic use. By

this regulation, this ruling is applicable to ophthalmic preparations that are regulated as drugs. By the regulation in §800.10 of this chapter, this ruling is applicable to ophthalmic preparations that are regulated as medical devices.

(3) The containers of ophthalmic preparations shall be sterile at the time of filling and closing, and the container or individual carton shall be so sealed that the contents cannot be used without destroying the seal. The packaging and labeling of ophthalmic preparations drugs shall also comply with §211.132 of this chapter on tamper-resistant packaging requirements.

that are over-the-counter

(b) Liquid ophthalmic preparations packed in multiple-dose containers should:

(1) Contain one or more suitable and harmless substances that will inhibit the growth of microorganisms; or

(2) Be so packaged as to volume and type of container and so labeled as to duration of use and with such necessary warnings as to afford adequate protection and minimize the hazard of injury resulting from contamination during use.

(c) Eye cups, eye droppers, and other dispensers intended for ophthalmic use should be sterile, and may be regarded as falling below their professed standard of purity or quality if they are not sterile. These articles, which are regulated as drugs if packaged with the drugs with which they are to be used, should be packaged so as to maintain sterility until the package is opened and be labeled, on or within the retail package, so as to afford adequate directions and necessary warnings to minimize the hazard of injury resulting from contamination during use.

[40 FR 13996, Mar. 27, 1975, as amended at 47 FR 50455, Nov. 5, 1982]

Subpart D [Reserved]

Subpart E-Prescription Drug
Consumer Price Listing

$200.200 Prescription drugs; reminder advertisements and reminder label

ing to provide price information to

consumers.

(a) Prescription drug reminder advertisements and reminder labeling intended to provide price information to consumers are exempt from the requirements of §§ 201 .100 and 202.1 of this chapter if all of the following conditions are met:

(1) The only purpose of the reminder advertisement or reminder labeling is to provide consumers with information concerning the price charged for a prescription for a particular drug product, and the reminder advertisement or reminder labeling contains no representation or suggestion concerning the drug product's safety, effectiveness, or indications for use.

(2) The reminder advertisement or reminder labeling contains the proprietary name of the drug product, if any; the established (generic) name of the drug product, if any; the drug product's strength if the product contains a single active ingredient or if the product contains more than one active ingredient and a relevant strength can be associated with the product without indicating each active ingredient (the established name and quantity of each active ingredient are not required); the dosage form; and the price charged for a prescription for a specific quantity of the drug product.

(3) The reminder advertisement or reminder labeling may also include other written, printed, or graphic matter, e.g., identification of professional or convenience services provided by the pharmacy: Provided, That such information is neither false nor misleading and contains no representation or suggestion concerning the drug product's safety, effectiveness, or indications for

use.