cgmp preamble 1978 - gmpeye
Transcript of cgmp preamble 1978 - gmpeye
Preamble to Current Good Manufacturing Practice in Manufacture, Processing, Packing, or Holding of Drugs
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VII. μ©μ΄ μ μ(DEFINITIONS)
The Commissioner received hundreds of comments regarding definitions. General
comments are listed immediately below; comments regarding specific definitions
follow in numerical order.
μ©μ΄ μ μμ κ΄λ ¨νμ¬ μλ°± 건μ μκ²¬μ΄ μ μλμλ€. μΌλ°μ μΈ μ견μ λ°λ‘ μλμ μμΌλ©°,
νΉμ μ©μ΄ μ μμ κ΄λ ¨λ μ견μ κ·Έ λ€μ μμλλ‘ μ 리νλ€.
50. One respondent said this section is inconsistent because certain terms such as
"drug" and "establishment" which are defined in the act are not defined here, while
other terms which are defined elsewhere are also defined here.
λ²μ μ μλμ΄ μλ "μμ½ν"κ³Ό "μμ€" κ°μ μΌλΆ μ©μ΄κ° μ¬κΈ°μλ μ μλμ΄ μμ§ μμΌλ©°,
λ€λ₯Έ κ³³μμ μ΄λ―Έ μ μλμ΄ μλ μ©μ΄κ° μ¬κΈ°μ λ€μ μ μλμ΄ μμ΄, μΌκ΄μ±μ΄ μλ€λ
μκ²¬μ΄ ν 건 μμλ€.
The Commissioner believes that the length of part 210 would be unnecessarily
increased by including in this part the definitions of terms that are well known or
already defined in the act. Other terms the meaning of which may not be as
readily recognized, or may vary in other regulations because of context and needs,
are defined in part 210 as a standard reference.
μ μλ €μ Έ μκ±°λ μ΄λ―Έ λ²μ μ μλμ΄ μλ μ©μ΄μ μ μλ₯Ό μ΄ ννΈμ ν¬ν¨μν€λ©΄, ννΈ
210μ΄ λΆνμνκ² κΈΈμ΄μ§ μ μλ€κ³ λ³Έλ€. μλ―Έκ° μ©μ΄νκ² μ΄ν΄λμ§ μκ±°λ μν©κ³Ό
νμμ λ°λΌ λ€λ₯Έ κ·μ μμ λ€λ₯΄κ² μ μλλ κΈ°ν μ©μ΄λ€μ ννΈ 210μμ μλ―Έλ₯Ό λͺ ννκ²
μ μνμ¬ κΈ°μ€μΌλ‘ μΌλλ‘ νλ€.
51. One comment suggested that all terms defined in part 210 be highlighted in the
running text.
ννΈ 210μ μ μλ λͺ¨λ μ©μ΄λ₯Ό λ³Έλ¬Έμμ κ°μ‘°νμ¬ νμν΄μΌ νλ€λ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner is not convinced that highlighting defined words in the running
text offers any advantages over the more usual manner of printing. For example,
some persons might interpret highlighting as adding emphasis that is not intended
to a particular word or phrase. This suggestion cannot be adopted.
μ©μ΄ μ μμ ν¬ν¨λ λ¨μ΄λ₯Ό λ³Έλ¬Έμμ λ€μ κ°μ‘°νμ¬ νκΈ°νλ κ²μ΄ ν΅μμ μΈ μΈμ λ°©μκ³Ό
λΉκ΅νμ¬ μ₯μ μ κ°λλ€κ³ μκ°νμ§ μλλ€. μλ₯Ό λ€μ΄ κ·Έλ¬ν κ°μ‘° ννμΌλ‘ μΈν΄, νΉμ
λ¨μ΄λ ꡬμ μ λνμ¬ μλνμ§ μμλ μλ―Έμ κ°μ‘°λ‘ ν΄μνλ μ¬λμ΄ μμ μ μλ€.
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κ·Έλ¬λ―λ‘ μ΄ μ μμ μ±ννμ§ μμλ€.
52. One respondent suggested rules for selecting words to be defined, namely: (1)
Words which will be used in a sense differing from that given in the currently
accepted dictionaries and (2) words whose meaning will be limited by the regulation.
μ©μ΄ μ μ λμ λ¨μ΄μ μ μ κ·μΉμ λ€μκ³Ό κ°μ΄ μ μν μκ²¬μ΄ ν 건 μμλ€. (1) νμ¬
λ리 μΈμ λλ μ¬μ μ μ μλ κ²κ³Ό λ€λ₯Έ μλ―Έλ‘ μ¬μ©λλ λ¨μ΄, (2) μ΄ κ·μ μμ μ νμ μΈ
μλ―Έλ‘ μ¬μ©λλ λ¨μ΄.
The Commissioner believes the above criteria have been generally used for
selecting terms to be defined. He does not wish, however, to limit strictly the
criteria for determining the terms to be defined in this part.
μ΄μ κ°μ κΈ°μ€μ μ©μ΄ μ μ λμ μ©μ΄μ μ μ μμ μΌλ°μ μΌλ‘ μ μ©νλ κ²μ΄λ€. νμ§λ§
μ΄ ννΈμ μ©μ΄ μ μ λμ μ©μ΄μ κ²°μ μ μ΄ κΈ°μ€μ μ격νκ² μ μ©ν μκ°μ μλ€.
53. Several comments asked that commonly used terms such as "drug product
containers," "labeling," and "production area" be defined.
"μμ½ν μ©κΈ°", "λΌλ²¨λ§", "μμ° μ§μ" κ°μ μΌλ°μ μΌλ‘ μ¬μ©λλ μ©μ΄μ μλ―Έλ μ μν΄μΌ
νλ€λ μκ²¬μ΄ λ€μ μμλ€.
The Commissioner finds that either the terms have already been defined elsewhere
(e.g., "labeling," which is defined in section 201(m) of the act) or they are generally
well understood and need no further definition (e.g., "drug product container"). He
concludes that no further definitions need to be added at this time.
κ·Έμ κ°μ μ©μ΄μ μλ―Έλ μ΄λ―Έ λ€λ₯Έ κ³³μ μ μλμ΄ μκ±°λ(μ, "λΌλ²¨λ§"μ λ² μΉμ
201(m)μ μ μλμ΄ μμ), μΌλ°μ μΌλ‘ κ·Έ μλ―Έκ° μΆ©λΆν μ΄ν΄λμ΄ λ μ΄μμ μ©μ΄ μ μκ°
νμ μλ€(μ, "μμ½ν μ©κΈ°")κ³ μκ°λλ€. κ·Έλ¬λ―λ‘ νμ¬λ μ©μ΄ μ μλ₯Ό μΆκ°ν νμκ°
μμ΄ λ³΄μΈλ€.
54. One comment suggested that "cycle of manufacture" be defined in 210.3(b)(2)
as "any period of time in which the batch is not adversely altered."
210.3(b)(2)μ "μ μ‘° μ¬μ΄ν΄"μ μΆκ°νκ³ κ·Έ μλ―Έλ₯Ό "λ°°μΉκ° λΆμ μ μΌλ‘ λ³νμ§ μλ
κΈ°κ°"μΌλ‘ μ μνμλ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner has considered this comment, but does not find that the
suggested wording offers any advantage. The definition, as it appeared in the
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proposal, has been in the CGMP regulations for a number of years. The
Commissioner is confident that this definition is well understood.
μ΄ μ견μ κ²ν νμΌλ, κ·Έλ¬ν μ©μ΄μ μΆκ°κ° μ΄λ€ μ΄μ μ΄ μμμ§ μ μ μλ€. κ°μ μμ
μ©μ΄ μ μλ μ΄λ―Έ λͺ λ λμ CGMP κ·μ μ μμλ κ²μ΄λ€. μ΄ μ©μ΄μ μλ―Έλ μ΄λ―Έ μΆ©λΆν
μ΄ν΄λκ³ μλ€κ³ μκ°νλ€.
55. Several comments suggested modification of the term "batch" in 210.3(b)(2) by
addition of the words "is intended to have" before "uniform character." Another
modification suggested was a new phrase at the end of the sentence: "Which is
accepted and offered for sale or distribution."
210.3(b)(2)μ "λ°°μΉ"μ λν μ©μ΄ μ μμ κ΄λ ¨νμ¬ "κ· μΌν νΉμ±" μμ "보μ νλλ‘
λ§λ€μ΄μ§"μ΄λ 문ꡬλ₯Ό μΆκ°νμλ μκ²¬μ΄ μμλ€. λν μ΄ λ¬Έμ₯ λ§μ§λ§μ "ν맀 λλ
μ ν΅μ μ ν©νκ³ μ΄λ₯Ό μν΄ μ 곡λλ"μ΄λΌλ 문ꡬλ₯Ό μ½μ νμλ μκ²¬μ΄ μμλ€.
In defining a "batch," the Commissioner has adopted the phrase "intended to have
uniform character and quality." Using the phrase "intended to have" in the
definition allows the use of the term "batch" without having to distinguish between
acceptable and unacceptable batches. If a manufactured batch does not have
uniform character and quality within specified limits, then the batch becomes an
unacceptable or a rejected batch. The Commissioner rejects the phrase "which is
accepted and offered for sale or distribution." Those batches which are
manufactured but never intended for sale or distribution may be designated as trial
or experimental batches by the manufacturer.
"λ°°μΉ"μ μ©μ΄ μ μμ κ΄λ ¨νμ¬ "κ· μΌν νΉμ±κ³Ό νμ§μ 보μ νλλ‘ λ§λ€μ΄μ§"μ΄λΌλ 문ꡬλ₯Ό
μ±ννκΈ°λ‘ νλ€. μ©μ΄ μ μμ "보μ νλλ‘ λ§λ€μ΄μ§"μ΄λΌλ ꡬμ μ μ½μ ν¨μΌλ‘μ¨, μ ν©
λ°°μΉμ λΆμ ν© λ°°μΉλ₯Ό ꡬλΆν νμ μμ΄, "λ°°μΉ"λΌλ μ©μ΄λ₯Ό μ¬μ©ν μ μκ² λλ€. μ μ‘°ν
λ°°μΉκ° μ§μ λ²μ μ΄λ΄μ κ· μΌν νΉμ±κ³Ό νμ§μ 보μ νμ§ μμΌλ©΄, κ·Έ λ°°μΉλ μμ© λΆκ°λ₯ν
λ°°μΉ λλ λΆμ ν© λ°°μΉκ° λλ€. "ν맀 λλ μ ν΅μ μ ν©νκ³ μ΄λ₯Ό μν΄ μ 곡λλ"μ΄λΌλ
ννμ μ½μ νμ§ μκΈ°λ‘ νλ€. μ μ‘°κ° λμμ§λ§ ν맀 λλ μ ν΅ν κ²μ΄ μλ λ°°μΉλ₯Ό
μ μ‘°μ μ²΄κ° μν λλ μ€ν λ°°μΉλ‘ μ§μ ν μ μλ€.
56. Three comments on 210.3(b)(3) requested that the term "component" be
changed to "ingredient," stating that the former term has been used in the drug
industry for "packaging supplies."
210.3(b)(3)μ μ©μ΄ μ μμ κ΄λ ¨νμ¬, "μλ£(component)"λ₯Ό "μ±λΆ(ingredient)"μΌλ‘
λ³κ²½νμλ μκ²¬μ΄ μΈ κ±΄ μμλ€. "μλ£(component)"λΌλ μμ΄ ννμ μ μ½ μ κ³μμ
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"ν¬μ₯ μμ¬"μ μ£Όλ‘ μ¬μ©νκ³ μκΈ° λλ¬Έμ΄λΌλ μ΄μ μμλ€.
The Commissioner recognizes that the term "component" is broadly used in the
English language and may have a variety of meanings. However, the definition of
this term in the proposal has been in effect for a number of years and the
Commissioner believes it is generally well understood. Because only three
comments were received regarding this particular issue, the Commissioner
concludes that the drug industry generally does not find the term misleading.
Therefore, the recommendation is not adopted.
"μλ£(component)"λΌλ μμ΄ λ¨μ΄κ° λ리 μ¬μ©λκ³ μμΌλ©°, κ·Έ μλ―Έλ λ€μν μ μλ€.
κ·Έλ¬λ μ΄ μ©μ΄ μ μλ μ€λ«λμ μ¬μ©λμ΄ μλ κ²μ΄λ©°, μΌλ°μ μΌλ‘ μ΄ν΄νλλ° λ¬΄λ¦¬κ°
μλ€κ³ μκ°νλ€. μ΄μ κ΄λ ¨νμ¬ 3κ° μ견λ§μ΄ μ μλμμΌλ―λ‘, μ μ½ μ κ³κ° μ΄ μ©μ΄μ
μλ―Έλ₯Ό μ΄ν΄νλλ° ν° λ¬Έμ κ° μλ€κ³ λ³Ό μ μλ€. κ·Έλ¬λ―λ‘ μ΄ μ견μ μ±ννμ§ μμλ€.
57. A suggestion was made that the definition for the word "component" in
210.3(b)(3) should include gases and filters, because these items need additional
control when used in the manufacture of injectable products.
210.3(b)(3)μ "μλ£"μ λν μ©μ΄ μ μμ κ°μ€μ νν°λ ν¬ν¨μμΌμΌ νλ€λ μ견μ΄
μμλ€. κ°μ€μ νν°λ μ£Όμ¬μ μ μ‘° μμ μΆκ°μ μΈ κ΄λ¦¬κ° νμνλ€λ μ΄μ μμμλ€.
The Commissioner notes that "component" includes gases that are used as
ingredients. He believes filters are more appropriately classified as equipment.
The Commissioner believes that control of gases and filters is adequately set out in
the regulations.
μ±λΆμΌλ‘ μ¬μ©λλ κ°μ€λ "μλ£"μ ν¬ν¨λλ€κ³ λ³Έλ€. λ°λ©΄ νν°λ μ€λΉλ‘ λΆλ₯νλ κ²μ΄
λ³΄λ€ μ μ νλ€κ³ μκ°νλ€. κ°μ€μ νν°μ κ΄λ¦¬ κΈ°μ€μ΄ κ·μ μ μ μ νκ² μ μλμ΄ μλ€κ³
μκ°νλ€.
58. One comment suggested that the definition for "component" be expanded to
include the phrase "raw material, chemical compound, drug substance or
pharmaceutic ingredient."
"μλ£"μ μ©μ΄ μ μλ₯Ό "μλ£ λ¬Όν, ννμ νν©λ¬Ό, μλ£μμ½ν λλ μ μ½ μ±λΆ"κΉμ§
ν¬ν¨νλ κ²μΌλ‘ νλν΄μΌ νλ€λ μκ²¬μ΄ μμλ€.
The Commissioner agrees that the above items when used as ingredients are
properly classed as components. It is not necessary or desirable, however, to list
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each type of material that may become a component under the regulations,
because items other than those identified in the comment may also be
"components." Therefore, the suggestion is not accepted.
μκΈ° λ¬Όνμ΄ μ±λΆμΌλ‘ μ¬μ©λλ€λ©΄ μλ£λ‘ λΆλ₯νλ κ²μ΄ μ μ νλ€κ³ μκ°νλ€. νμ§λ§
μλ£μ ν΄λΉλλ μ΄λ€ λ¬Όν κ°κ°μ μ νμ μ΄κ±°ν νμλ μκ±°λ λ°λμ§νμ§ μλ€. μ견μ
μ μλ κ² μ΄μΈμ λ€λ₯Έ λ¬Όνλ "μλ£"κ° λ μ μκΈ° λλ¬Έμ΄λ€. κ·Έλ¬λ―λ‘ μ΄ μ견μ
μ±ννμ§ μμλ€.
59. A suggestion was received to include the following phrase after the word
"manufacture" in the second sentence of 210.3(b)(3): "of finished dosage form, e.g.
tablets, capsules, solutions, etc."
210.3(b)(3)μ λ λ²μ§Έ λ¬Έμ₯ κ°μ΄λ° "μ μ‘°"λΌλ λ¨μ΄ λ€μ "μ΅μ’ μ ν, μλ₯Ό λ€μ΄ μ μ ,
μΊ‘μμ , μ‘μ λ±μ"λΌλ 문ꡬλ₯Ό ν¬ν¨μν€μλ μκ²¬μ΄ μμλ€.
The Commissioner rejects this suggestion. The term "drug product" is defined in
paragraph (b)(4) of 210.3 as "a finished dosage form" and restatement of the
definition is inappropriate.
μ΄ μ μμ μμ©νμ§ μμλ€. "μμ½ν"μ 210.3μ (b)(4)μ "μ΅μ’ μ ν"μΌλ‘ μ μλμ΄
μμΌλ©°, μ΄λ₯Ό λ€μ λ°λ³΅νλ κ²μ μ μ νμ§ μκΈ° λλ¬Έμ΄λ€.
60. Several comments requested clarification of the relationship among the
definitions in 210.3(b) (3), (7), and (8) of "component," "active ingredient," and
"inactive ingredient." Comments expressed concern that proposed definitions of the
types of ingredients do not include all materials contemplated under the definition
of "component."
210.3(b)(3), (7), (8)μ "μλ£", "νμ± μ±λΆ", "λΉνμ± μ±λΆ"μ κ΄κ³λ₯Ό λͺ νν ν΄λ¬λΌλ
μμ²μ΄ λ€μ μμλ€. "μλ£"μ μ©μ΄ μ μμμ μ μν λͺ¨λ λ¬Όνμ΄ μ νλ³ μ±λΆμ μ©μ΄
μ μμ ν¬ν¨λμ§ μμλ€λ μκ²¬μ΄ μμλ€.
The Commissioner finds that the definition for "inactive ingredient" in 210.3(b)(8)
should be modified so that it clearly includes "any component other than an active
ingredient." He believes this change will eliminate any misunderstanding of these
definitions.
210.3(b)(8)μ "λΉνμ± μ±λΆ" μ©μ΄ μ μλ₯Ό μμ νμ¬ "νμ± μ±λΆ μ΄μΈμ κΈ°ν μλ£"λ‘
λͺ νν νλ€. μ΄μ λ°λΌ μ©μ΄μ νΌλμ΄ μμ΄μ§ κ²μΌλ‘ μκ°λλ€.
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61. One comment suggested that the term "drug product," as proposed in
210.3(b)(4), could be interpreted to mean only the finished packaged unit.
210.3(b)(4)μ "μμ½ν"μ μ΅μ’ ν¬μ₯ λ¨μλ§ μλ―Ένλ κ²μΌλ‘ ν΄μλ μ μλ€λ μκ²¬μ΄ ν
건 μμλ€.
The Commissioner finds that the term is defined as meaning "finished dosage form"
regardless of whether it is in package form.
"μμ½ν"μ ν¬μ₯ μνμ μκ΄μμ΄ "μ΅μ’ μ ν"μ μλ―Ένλ κ²μ΄λ€.
62. A comment was received stating that the term "drug product" as defined in
210.3(b)(4) excludes placebos because the definition includes the phrase "active
drug ingredient."
210.3(b)(4)μ "μμ½ν" μ©μ΄ μ μμλ "νμ± μ½ν μ±λΆ"μ΄λΌλ ννμ΄ ν¬ν¨λμ΄ μμ΄,
μμ½μ μμ½νμμ μ μΈλλ€λ μκ²¬μ΄ μμλ€.
The intended use of placebos in medical treatment is to bring about a therapeutic
effect, without a pharmacologically active agent, because of the psychic effect in
some patients that may produce symptomatic relief. In addition, it is often used as
a control in clinical trials for new drugs. Even though the chemicals from which the
placebos are made are not intended to cause a direct pharmacologic response, the
maintenance of their quality is important because of their use in patients,
particularly in controlled drug studies. By its use, a placebo meets the definition of
a "drug" contained in section 201(g) of the act. Therefore, to eliminate any doubt
whether these regulations apply to placebos, the Commissioner has revised the
definition to include them specifically.
μνμ μΉλ£μμ μμ½μ μ©λλ, μ½λ¦¬νμ νμ± μμ μμ΄ μΉλ£ ν¨κ³Όλ₯Ό μ λ°νλλ° μλ€.
μΌλΆ νμμμλ μ¬λ¦¬μ μν₯λ§μΌλ‘ μ¦μ μνκ° λνλ μ μκΈ° λλ¬Έμ΄λ€. μ΄μΈμλ μ μ½
μμ μν μμ λμ‘°μ½μΌλ‘ μ¬μ©λκΈ°λ νλ€. μμ½μ λ§λλ νν λ¬Όμ§μ΄ μ§μ μ μΌλ‘
μ½λ¦¬νμ λ°μμ μ λ°νκΈ° μν κ²μ μλλλΌλ, μμ½μ νμ, νΉν λμ‘° μμ μνμ
μ°Έμ¬νλ νμμκ² ν¬μ¬λλ―λ‘ μμ½μ νμ§ μ μ§λ μ€μνλ€. κ²°κ΅ μμ½μ κ·Έμ μ©λμ
μνμ¬ λ² μΉμ 201(g)μ "μμ½ν" μ©μ΄ μ μμ λΆν©νλ€. κ·Έλ¬λ―λ‘ μ΄ κ·μ μ΄ μμ½μλ
μ μ©λλμ§ μ¬λΆμ λν λ Όλμ μ¬μ§λ₯Ό μμ κΈ° μν΄, μ΄ λΆλΆλ ꡬ체μ μΌλ‘ ν¬ν¨νλλ‘
μμ νλ€.
63. A number of comments questioned the definition of "fiber" in proposed
210.3(b)(5). The comments were that "fiber" had been defined arbitrarily and
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without scientific basis; that the definition was too general and could include, for
example, crystal, metal and splintered wood; and that the definition should include
dimensional parameters for the fiber size. Comments recommended that the
definition include morphological descriptions such as threadlike, filamentous,
amorphous or noncrystalline, cellular, foreign, and hairlike. Several comments
recommended that the American Society for Testing and Materials definition be
used. Others suggested that a length of at least 100 microns and a length/width
ratio of 10 to 1 be adopted. One comment called for adopting a minimum length
of 10 microns and a diameter one-tenth the length.
210.3(b)(5)μ "μ¬μ "μ λν μ©μ΄ μ μμ κ΄λ ¨νμ¬ λ§μ μκ²¬μ΄ μ μλμλ€. μ£Όλ‘
"μ¬μ "μ μλ―Έλ₯Ό κ³Όνμ κ·Όκ±° μμ΄ μμμ μΌλ‘ μ νλ€λ μ견μ΄μλ€. μ΄ μ©μ΄ μ μλ λ무
μΌλ°μ μ΄λ©°, μλ₯Ό λ€μ΄ κ²°μ , κΈμ, λ무 μ‘°κ°λ μ΄ μ μμ ν΄λΉλ μ μλ€λ κ²μ΄λ€. λν
μ¬μ μ ν¬κΈ°μ λν κΈ°μ€μ ν¬ν¨μμΌμΌ νλ€κ³ νλ€. μ΄ μ©μ΄ μ μμ νννμ μ€λͺ (μ, μ€
κ°μ, νλΌλ©νΈμ±, λΆμ ν λλ λΉκ²°μ ν, μΈν¬μ±, μΈλμ±, λ¨Έλ¦¬μΉ΄λ½ κ°μ)μ ν¬ν¨μν€μλ
μκ²¬μ΄ μμλ€. ASTM(American Society for Testing and Materials)μ μ©μ΄ μ μλ₯Ό
μ¬μ©νμλ μ견λ λ€μ μμλ€. λν κΈΈμ΄κ° μ΅μν 100 λ§μ΄ν¬λ‘ μ΄κ³ κΈΈμ΄/λμ΄ λΉμ¨μ΄
10:1μΈ κ²μ μ¬μ λ‘ νμλ μ μλ μμλ€. μ΅μ κΈΈμ΄κ° 10 λ§μ΄ν¬λ‘ μ΄κ³ μ§κ²½μ΄ κΈΈμ΄μ
1/10μΈ κ²μ μ¬μ λ‘ νμλ μ견λ ν 건 μμλ€.
The Commissioner finds that the term "fiber" has not been defined arbitrarily and
without scientific basis. The basis for the fiber definition was discussed in the final
regulations for asbestos-form particles in drugs for parenteral injection, which
appeared in the FEDERAL REGISTER of March 14, 1975 (40 FR 11865). (Those final
regulations reference the definition of "fiber" appearing in "Occupational Exposure
to Asbestos," criteria document, U.S. Public Health Service, National Institute for
Occupational Safety and Health, Chapter VIII, p. 6, 1972). The Commissioner
believes that the definition should be as broad as possible and that the suggested
morphological descriptions and dimensional parameters are unnecessary and in
many instances are not informative. Dimensional parameters were intentionally
left out because current knowledge is limited as to what size fiber does not
constitute a hazard. Furthermore, the suggested fiber length of at least 100
microns is unacceptable because most asbestos fibers released from asbestos-
cellulose filters are less than 70 microns in length.
"μ¬μ "μ μ©μ΄ μ μκ° κ³Όνμ κ·Όκ±° μμ΄ μμλ‘ μ€μ λμλ€κ³ μκ°νμ§ μλλ€. μ¬μ μ
μ©μ΄ μ μμ λν κ·Όκ±°λ 1975λ 3μ 14μΌμ μ°λ°©κ΄λ³΄(40 FR 11865)μ κ²μ¬λ μ£Όμ¬μ
μ€μ μλ©΄ μ μμ λν μ΅μ’ κ·μ μμ μ€λͺ νλ€. (μ΄ μ΅μ’ κ·μ μ "μ§μ μ μλ©΄ λ ΈμΆ" κΈ°μ€
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λ¬Έμ(U.S. Public Health Service, National Institute for Occupational Safety and
Health, Chapter VIII, p. 6, 1972)μ μ μλ "μ¬μ "μ μ©μ΄ μ μλ₯Ό μ°Έμ‘°νλ€.) μ΄ μ©μ΄
μ μλ κ°λ₯ν λκ² ν΄μΌ νλ©°, μ견μμ μ μν νννμ μ€λͺ κ³Ό ν¬κΈ° κΈ°μ€μ λΆνμνλ©°
λ§μ κ²½μ°μ λμμ΄ λμ§ μλλ€κ³ μκ°νλ€. νμ¬μ μ§μμΌλ‘λ μ΄λ μ λ ν¬κΈ°μ μ¬μ κ°
μννμ§ μμμ§ μ νν μ μ μκΈ° λλ¬Έμ, ν¬κΈ° κΈ°μ€μ μλμ μΌλ‘ λ°°μ νλ€. λν μ΅μ
100 λ§μ΄ν¬λ‘ μ μ¬μ κΈΈμ΄λ μΈμ ν μ μλ€. μλ©΄-μ λ£°λ‘μ€μ€ νν°μμ λ°©μΆλλ λλ€μ
μλ©΄ μ¬μ λ κΈΈμ΄κ° 70 λ§μ΄ν¬λ‘ μ΄νμ΄κΈ° λλ¬Έμ΄λ€.
The American Society for Testing and Materials' specifications (ASTM Manual F24-65,
Standard Methods for Measuring and Counting Particulate Contamination on
Surfaces) for defining "fiber" are not pertinent to the subject at hand. They were
developed specifically for particles on surfaces of mechanical objects as related to
abrasion of such objects.
"μ¬μ "μ μ©μ΄ μ μκ° μ μλ ASTM κ·κ²©(ASTM Manual F24-65, Standard Methods for
Measuring and Counting Particulate Contamination on Surfaces)μ μ΄ μ£Όμ μ
κ΄λ ¨μ±μ΄ μλ€. μ΄ κ·κ²©μ κΈ°κ³μ λ§λͺ¨μ κ΄λ ¨νμ¬, κΈ°κ³ νλ©΄μ μ μλ₯Ό λμμΌλ‘ κ°λ°λ
κ²μ΄κΈ° λλ¬Έμ΄λ€.
To eliminate any concern that the definition of fiber would include particles
intentionally present, as in drug suspensions, the final regulation is modified by
adopting the concept of particle contamination. Therefore, fiber means any
particulate contaminate having a length at least three times its width.
ννμ‘μ κ²½μ°μ κ°μ΄ μλμ μΌλ‘ μ‘΄μ¬νλ μ μλ μ¬μ μ μ μμ ν¬ν¨λ μ μλ€λ μ°λ €λ₯Ό
ν΄μνκΈ° μν΄, 미립μ μ€μΌμ κ°λ μ μ±ννμ¬ μ΅μ’ κ·μ μ μμ νλ€. κ·Έλ¬λ―λ‘ μ¬μ λ
κΈΈμ΄κ° λμ΄μ 3λ°° μ΄μμΈ λͺ¨λ μ μμ± μ€μΌ λ¬Όμ§μ μλ―Ένλ€.
64. Comment was received regarding 210.3(b)(6) that the definition for "non-fiber-
releasing filter" should include the concept of a filter "being designed" not to
release fibers after appropriate pretreatment. Another comment said a
requirement for non-release of fibers is unrealistically absolute, i.e., no known filter
could meet the definition.
210.3(b)(6)μ "μ¬μ λΉλ°©μΆ νν°"μ κ΄λ ¨νμ¬, μ μ ν μ μ²λ¦¬ μ΄νμ μ¬μ λ₯Ό λ°©μΆνμ§
μλλ‘ "μ€κ³λ" νν°λ μ¬κΈ°μ ν¬ν¨μμΌμΌ νλ€λ μκ²¬μ΄ μμλ€. λν μ¬μ μ λΉλ°©μΆ
κΈ°μ€μ΄ λΉνμ€μ μΌλ‘ μ λμ μΈ κ²μ΄λΌλ μ견λ μμλ€. μ΄ μ©μ΄ μ μμ λΆν©ν μ μλ
νν°λ μλ€λ κ²μ΄λ€.
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The Commissioner advises that the final regulation adopting the definition for "non-
fiber-releasing filter," published in the FEDERAL REGISTER of March 14, 1975 (40
FR 11865), addressed similar issues. In responding to comments in that document,
the Commissioner concluded the definition should include the concept that after
appropriate pretreatment such as washing or flushing, the filter will not continue to
release fibers into the drug that is being filtered. The design concept is therefore
taken into account because of the distinction made between filters which release
fibers by media migration, i.e., continuous release due to the nature of the filter,
and filters which contain fibers from structural supports and contamination.
1975λ 3μ 14μΌμ μ°λ°©κ΄λ³΄(40 FR 11865)μ κ²μ¬λ, "μ¬μ λΉλ°©μΆ νν°"μ μ©μ΄ μ μλ₯Ό
μ±νν μ΅μ’ κ·μ μμ μ΄μ μ μ¬ν μ¬μμ λ€λ£¬ μ μ΄ μλ€. μ΄λλ μ΄λ¬ν μ견과 κ΄λ ¨νμ¬,
μ μ ν μ μ²λ¦¬(μ, μΈμ² λλ νλ¬μ±) μ΄νμ νν°κ° μ¬κ³Ό λμ μμ½νμ μ¬μ λ₯Ό κ³μ
λ°©μΆνμ§ μλλ€λ κ°λ μ μ©μ΄ μ μμ ν¬ν¨μμΌμΌ νλ€κ³ κ²°λ‘ λ΄λ Έλ€. κ·Έλ¬λ―λ‘ "맀체
μ΄λ" λλ¬Έμ μ¬μ κ° λ°©μΆλλ νν°(μ¦, νν°μ νΉμ±μΌλ‘ μΈν μ§μμ λ°©μΆ)μ ꡬ쑰μ
μ§μ§μ μ€μΌμμ μ λν μ¬μ κ° μλ νν°λ₯Ό ꡬλΆν νμκ° μμ΄, μ΄ λμμΈ κ°λ μ
κ³ λ €νλ€.
With regard to the comment that the requirement for non-release of fibers is
unrealistically absolute, the Commissioner finds that the definition clearly describes
types of fibers that are relied upon in the industry as "non-fiber releasing." The
Commissioner concedes that any filter may release an occasional particle, some of
which may meet the definition of "fiber" under 210.3(b)(5). The purpose of the
definition for "non-fiber releasing filter," which has been applied for over 2 years
without apparent misunderstanding, is to provide a reasonable and practical
description of a filter that may be fabricated from a number of different materials
and will not, in the ordinary sense, introduce fibers into the drug product during
filtration.
μ¬μ λΉλ°©μΆ κΈ°μ€μ΄ λΉνμ€μ μΌλ‘ μ λμ μΈ κ²μ΄λΌλ μ견과 κ΄λ ¨νμ¬ μ€λͺ νλ©΄, μ©μ΄
μ μμλ μ κ³μμ "μ¬μ λΉλ°©μΆ"μ μλ―Έλ₯Ό νμ νλλ° λμμ΄ λλ μ¬μ μ μ νμ΄
λͺ ννκ² κΈ°μ λμ΄ μλ€. μ΄λ ν νν°λ λλ‘λ 미립μλ₯Ό λ°©μΆν μ μμΌλ©°, μ΄ κ°μ΄λ°
μΌλΆλ 210.3(b)(5)μ "μ¬μ "μ ν΄λΉλ μ μλ€. λλ ·ν μ€ν΄ μμ΄ 2λ λκ² μ μ©λμ΄ μ¨
"μ¬μ λΉλ°©μΆ νν°" μ©μ΄ μ μμ λͺ©μ μ, μλ§μ λ€μν μ¬μ§λ‘ μ μλλ©° μΌλ°μ μΈ
μλ―Έμμ μ¬κ³Ό μ€μ μμ½νμ μ¬μ λ₯Ό λμ μν€μ§ μλ νν°λ₯Ό ν©λ¦¬μ μ΄κ³ μ€μ μ μΌλ‘
κΈ°μ νλλ° μλ€.
As discussed in detail in the preamble to the March 14, 1975 final regulation
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adopting the definitions for "fiber" and "non-fiber releasing filter", FDA is studying
several issues involving fiber contamination and the effects on humans to fiber
exposure. Until such time as the Commissioner has obtained sufficient information
to alter his position on fiber contamination in parenteral drug products without
adversely affecting the public health, he concludes that the definition for "non-fiber
releasing filter" continues to be appropriate for these regulations.
"μ¬μ "μ "μ¬μ λΉλ°©μΆ νν°"μ μ©μ΄ μ μλ₯Ό μ±νν 1975λ 3μ 14μΌμ μ΅μ’ κ·μ
μ λ¬Έμμ μμΈν μ€λͺ ν λ°μ κ°μ΄, FDAλ μ¬μ μ€μΌ λ° μ¬μ λ ΈμΆμ΄ μ¬λμ λ―ΈμΉλ
μν₯κ³Ό κ΄λ ¨ν μ¬λ¬ κ°μ§ μ¬νμ μ‘°μ¬νκ³ μλ€. μΆ©λΆν μ 보λ₯Ό ν보νμ¬ κ³΅μ€ λ³΄κ±΄μ
λΆμ μ μΈ μν₯μ μ£Όμ§ μμΌλ©΄μ μ£Όμ¬μ μ μ¬μ μ€μΌμ λν μ μ₯μ λ°κΏ μ μλ μκΈ°κ° λ
λκΉμ§λ, μ΄ κ·μ μ "μ¬μ λΉλ°©μΆ νν°" μ©μ΄ μ μκ° κ³μ μ μ νλ€κ³ μκ°λλ€.
65. Comment was received that the definition of "non-fiber-releasing filter" as
written in 210.3(a)(6) would discourage the development of asbestos filters that
might not be fiber releasing.
210.3(a)(6)μ "μ¬μ λΉλ°©μΆ νν°" μ©μ΄ μ μλ μ¬μ λ₯Ό λ°©μΆνμ§ μλ μλ©΄ νν°μ κ°λ°μ
μ΅μ ν μ μλ€λ μκ²¬μ΄ μμλ€.
The Commissioner advises that it is not the intention of FDA to discourage the
development of asbestos filters. In this regard, the preamble to the final order in
the FEDERAL REGISTER of March 14, 1975 (40 FR 11865) addresses this issue in
detail.
μλ©΄ νν°μ κ°λ°μ μ΅μ νλ κ²μ΄ FDAμ μλλ μλλ€. 1975λ 3μ 14μΌμ
μ°λ°©κ΄λ³΄(40 FR 11865)μ κ²μ¬λ μ΅μ’ λͺ λ Ή μ λ¬Έμ μ΄μ κ΄λ ¨λ μ¬νμ΄ μμΈν κΈ°μ λμ΄
μλ€.
66. One comment suggested that "non-fiber-releasing filter" be redefined to apply
only to the final filtration of components and drug products.
μλ£μ μμ½νμ μ΅μ’ μ¬κ³Όμλ§ μ μ©νλλ‘, "μ¬μ λΉλ°©μΆ νν°"μ μλ―Έλ₯Ό λ€μ μ μν΄μΌ
νλ€λ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner concludes that the suggestion would allow use of an asbestos
filter for filtration of in-process materials. This use of asbestos filters is
unacceptable, except under the provision of 211.72(b), and would defeat the
purpose of the regulation.
μ΄ μ견μ λ°λ₯΄λ©΄ μλ©΄ νν°λ₯Ό 곡μ λ¬Όν μ¬κ³Όμ μ¬μ©ν μ μκ² λλ€. 211.72(b)μ μν
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κ²½μ°λ₯Ό μ μΈνλ©΄, μλ©΄ νν°μ μ¬μ©μ μΈμ ν μ μμΌλ©° μ΄ κ·μ μ λͺ©μ μ λ§μ§ μλ€.
67. A comment suggested that after the word "component" in 210.3(b)(7) the
phrase "other than veterinary biological immunizing or diagnostic agent" should be
added.
210.3(b)(7)μ "μλ£" λ€μ "λλ¬Όμ© μλ¬Όνμ λ©΄μ λλ μ§λ¨ μΈμ μ΄μΈ"λ₯Ό μΆκ°ν΄μΌ
νλ€λ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner finds that articles that are not deemed drug products or that are
not under the jurisdiction of the act are not subject to these regulations. It is not
desirable or feasible to identify in these regulations every specific class of articles
that are not subject to CGMP regulations. Veterinary biologicals have, however,
been excluded by changes in 210.2. When an interested person has a question
regarding the status of another individual product or class of products (for example,
the status of an article that may be either a drug or a device), that person may
obtain a formal opinion from FDA pursuant to 21 CFR 10.85.
μμ½νμΌλ‘ κ°μ£Όλμ§ μλ λ¬Όνμ΄λ λ²μ μ μ© λ²μμ μνμ§ μλ λ¬Όνμ μ΄ κ·μ μ
λμμ΄ μλλ€. CGMP κ·μ μ λμμ΄ μλ λͺ¨λ νΉμ λ¬Όνκ΅°μ μ΄ κ·μ μμ κ±°λ‘ νλ κ²μ
λ°λμ§νμ§λ μκ³ κ°λ₯νμ§λ μλ€. νμ§λ§ λλ¬Όμ© μλ¬Όνμ μ μ λ 210.2μ λ³κ²½μ μν΄
μ μΈλμλ€. λ€λ₯Έ μ ν λλ μ νκ΅°μ μνμ κ΄λ ¨νμ¬ μ§λ¬Έμ΄ μλ μ¬λμ(μ, μμ½ν
λλ μλ£κΈ°κΈ°μΌ μ μλ λ¬Όνμ μν), 21 CFR 10.85μ λ°λΌ FDAμ 곡μ μ견μ μμ²ν
μ μλ€.
68. Several comments asked that limits be placed on the term "in-process
materials" defined in 210.3(b)(9) in order to restrict it to those materials generated
"in-plant" as opposed to those materials acquired from an outside source.
μΈλΆμμ ν보ν λ¬Όνκ³Ό "곡μ₯ λ΄λΆ"μμ λ§λ λ¬Όνμ ꡬλΆνμ¬ μ체μ μΌλ‘ μ μ‘°ν
λ¬Όνμλ§ μ μ©νλλ‘, 210.3(b)(9)μ "곡μ λ¬Όν"μ κΈ°μ€μ μ ν΄ λμμΌ νλ€λ μ견μ΄
λ€μ μμλ€.
The Commissioner agrees that the term "in-process materials" is intended to apply
to materials being processed by establishments engaged in the preparation of a
drug product. He believes this intent is clear when the term is considered in the
scope of these regulations and that no change is needed.
"곡μ λ¬Όν"μ΄ μμ½ν μ μ‘°μ κ΄μ¬νλ μμ€μ΄ κ°κ³΅νλ λ¬Όνμ μ μ©λλ κ²μ΄λΌλ μ μ
λμνλ€. μ΄ κ·μ μ μ μ© λ²μλ₯Ό κ°μνμ¬ μκ°νλ©΄ μ΄ μλκ° λͺ νν μ μλμ΄ μλ€κ³
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μκ°νλ―λ‘ μ΄λ ν λ³κ²½λ νμνμ§ μλ€.
69. Several comments requested clarification whether the term "in-process
materials" in 210.3(b)(9) includes labels printed "in-house" and other
"nonchemical" items.
210.3(b)(9)μ "곡μ λ¬Όν"μ "μ체μ μΌλ‘" μΈμν λΌλ²¨κ³Ό κΈ°ν "λΉννμ " λ¬Όνλ
ν¬ν¨λλμ§ λͺ νν ν΄λ¬λΌλ μμ²μ΄ μμλ€.
It was not the Commissioner's intent that "in-process materials" include label
printing. The regulations do not suggest that such labeling would constitute in-
process materials. References to labeling materials are clearly stated in these
regulations when appropriate.
"곡μ λ¬Όν"μ λΌλ²¨ μΈμλ ν¬ν¨λμ§ μλλ€. κ·Έλ¬ν λΌλ²¨λ§ μμ¬κ° 곡μ λ¬Όνμ ν΄λΉλ μ
μλ€λ ννμ μ΄λμλ μλ€. μ μ ν κ²½μ°μ κ·μ μμ λΌλ²¨λ§ μμ¬λ₯Ό λͺ ννκ² μΈκΈνλ€.
70. One comment suggested that the word "materials" in 210.3(b)(9) be changed
to "ingredients."
210.3(b)(9)μμ "λ¬Όν"μ΄λ λ¨μ΄λ₯Ό "μ±λΆ"μΌλ‘ λ³κ²½ν΄μΌ νλ€λ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner concludes that the term "in-process materials" is in current
usage and sees no advantage to introducing the suggested term "in-process"
ingredients."
"곡μ λ¬Όν"μ΄λΌλ ννμ νμ¬ μ¬μ©νλ κ²μ΄λ©°, "곡μ μ±λΆ"μ΄λΌλ ννμ΄ λ λ«λ€κ³
보기 μ΄λ ΅λ€.
70a. One comment stated that 210.3(b)(9), and especially the word "fabricated" is
unclear and should be further defined to eliminate any possible confusion.
210.3(b)(9)μμ "μ‘°ν©"μ΄λΌλ λ¨μ΄μ μλ―Έκ° λͺ ννμ§ μμΌλ―λ‘ νΌλμ νΌνκΈ° μν΄ λ
μ νν μ μν΄μΌ νλ€λ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner does not agree that the word "fabricated" is unclear when used
in this definition. This suggestion is rejected because a broad term such as
"fabricated" is appropriate here.
μ΄ μ©μ΄ μ μμμ "μ‘°ν©"μ΄λΌλ λ¨μ΄μ μλ―Έκ° λͺ ννμ§ μλ€κ³ μκ°νμ§ μλλ€. μ¬κΈ°μλ
"μ‘°ν©" κ°μ λμ μλ―Έμ μ©μ΄κ° μ μ νκΈ° λλ¬Έμ μ΄ μ μμ μμ©νμ§ μμλ€.
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71. Several comments said, in the case of biologics, a "lot" may consist of more
than one batch and suggested that this be included in the definition of "lot" in
210.3(b)(10).
μλ¬Όνμ μ μ μΈ κ²½μ°μλ "λ‘νΈ"κ° νλ μ΄μμ λ°°μΉλ‘ ꡬμ±λ μ μμΌλ―λ‘,
210.3(b)(10)μ "λ‘νΈ"μ λν μ©μ΄ μ μμ μ΄ λΆλΆμ ν¬ν¨μν€μλ μκ²¬μ΄ λ€μ μμλ€.
Because the term "lot" has already been defined specifically for biological products
in 21 CFR 600.3(x), the Commissioner does not believe that any modification of the
definition in this part is appropriate. As previously indicated, the more specific
regulations for biological drug products take precedent over the more general.
μλ¬Όνμ μ μ μ "λ‘νΈ"μ λν μ©μ΄ μ μλ μ΄λ―Έ 21 CFR 600.3(x)μ ꡬ체μ μΌλ‘ μ μλμ΄
μμΌλ―λ‘, μ΄ ννΈμμ κ΅³μ΄ "λ‘νΈ"μ μ©μ΄ μ μλ₯Ό μμ ν νμκ° μλ€κ³ μκ°νλ€. μμ
μ€λͺ ν λ°μ κ°μ΄, μλ¬Όνμ μμ½νμ λμμΌλ‘ νλ λ³΄λ€ κ΅¬μ²΄μ μΈ κ·μ μ΄ λ€μ μΌλ°μ μΈ
κ²λ³΄λ€ μ°μ κΆμ κ°λλ€.
72. Two comments said the term "lot" was used elsewhere in the CGMP regulations
(e.g., 211.84(a)) to refer to containers and closures, which are neither drugs nor
drug products. They said either the definition in 210.3(b)(10) or the reference was
incorrect.
CGMP κ·μ μ λ€λ₯Έ κ³³μμ(μ, 211.84(a)) "λ‘νΈ"κ° μμ½νμ΄ μλ μ©κΈ°/λ§κ°μ κ΄λ ¨νμ¬
μ¬μ©λκ³ μλ€κ³ μ§μ ν μκ²¬μ΄ λ 건 μμλ€. μ΄λ€μ 210.3(b)(10)μ μ©μ΄ μ μκ°
μλͺ»λμκ±°λ λ€λ₯Έ κ³³μ "λ‘νΈ" νκΈ°κ° μλͺ»λμλ€κ³ λ§νλ€.
The Commissioner notes that the definition in 210.3(b)(10) refers to the term "drug
product," but does not limit to drug products the applications of the definition for
"lot." However, the proposed definition for "batch" is limited to drugs. Because a
lot is defined as a batch or portion of a batch, the definition for "batch" is expanded
to include materials other than drugs. Similarly, the definition for "lot number" is
expanded to include other materials.
210.3(b)(10)μ μ©μ΄ μ μλ "μμ½ν"μ κ΄ν κ²μ΄μ§λ§, "λ‘νΈ"μ μλ―Έλ₯Ό μμ½νμλ§
μ μ©νλ κ²μΌλ‘ μ ννκ³ μμ§ μλ€. νμ§λ§ "λ°°μΉ"μ μ©μ΄ μ μλ μμ½νμ κ΅νλλ€.
λ‘νΈλ ν λ°°μΉ λλ ν λ°°μΉμ μΌλΆλ‘ μ μλλ―λ‘, "λ°°μΉ"μ μ©μ΄ μ μλ μμ½ν μ΄μΈμ
λ€λ₯Έ λ¬ΌνκΉμ§ νλλλ€. λ§μ°¬κ°μ§λ‘ "λ‘νΈ λ²νΈ"μ μ μλ λ€λ₯Έ λ¬Όνλ ν¬ν¨νλ κ²μΌλ‘
νλλλ€.
73. One comment said the definition for "lot number" in 210.3(b)(11) unnecessarily
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ruled out the use of symbols.
210.3(b)(11)μ "λ‘νΈ λ²νΈ"λ κΈ°νΈμ μ¬μ©μ λΆνμνκ² λ°°μ νκ³ μλ€κ³ μ§μ ν μ견μ΄
ν 건 μμλ€.
It was not the Commissioner's intent to preclude the use of symbols, and the
definition is modified accordingly.
κΈ°νΈμ μ¬μ©μ λ°°μ ν μλλ μμΌλ©°, μ΄ μ©μ΄ μ μλ κ·Έμ λ°λΌ μμ νλ€.
74. One comment suggested deletion of the word "complete" from 210.3(b)(11) as
superfluous and subject to interpretation.
210.3(b)(11)μ μ©μ΄ μ μμμ "μ 체"λ λΆνμνλ©° μ¬λμ λ°λΌ λ€λ₯΄κ² ν΄μλ μ μκΈ°
λλ¬Έμ μμ ν΄μΌ νλ€λ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner finds that use of the phrase "complete history" emphasizes that
pertinent identifying information is included.
"μ 체 μ΄λ ₯"μ κ΄λ ¨ μλ³ μ λ³΄κ° ν¬ν¨λμ΄μΌ ν¨μ κ°μ‘°ν κ²μ΄λ€.
75. Two comments suggested that the words "testing, and quality control of drug
products" be deleted from the definition in 210.3(b)(12). One said these functions
do not belong in this definition because they introduce ambiguities elsewhere in the
proposed regulations. Examples given are: (1) 211.103, which requires yield
determination at the end of each distinct phase of manufacturing; and (2)
211.67(b), which requires that procedures describe a cleaning schedule for all
equipment used in manufacturing, processing, packaging, or holding of a drug
product. The respondent said yield calculations and cleaning schedules do not apply
to laboratory testing and equipment. Another respondent said the words "testing
and quality control of drug products" should be deleted because they conflict with
the concept of independent responsibility for quality control and manufacturing
functions.
210.3(b)(12)μμ "μμ½νμ μν, νμ§ κ΄λ¦¬"λ₯Ό μμ ν΄μΌ νλ€λ μκ²¬μ΄ λ 건 μμλ€.
μ΄ λ λΆλΆ λλ¬Έμ κ·μ μ λ€λ₯Έ κ³³μμ λͺ ννμ§ μμ κ²μ΄ λ°μν μ μκΈ° λλ¬Έμ μ΄ λ
μ 무λ₯Ό μ΄ μ©μ΄ μ μμ λμ§ λ§μμΌ νλ€λ κ²μ΄λ€. μ) (1) 211.103μ κ°κ°μ λλ ·ν
μ μ‘° λ¨κ³κ° λλλ©΄ μμ¨μ κ³μ°νλλ‘ μꡬνκ³ μμΌλ©°, (2) 211.67(b)λ μμ½νμ μ μ‘°,
κ°κ³΅, ν¬μ₯, λλ 보κ΄μ μ¬μ©λλ λͺ¨λ μ€λΉμ λν μΈμ² μΌμ μ μ μ°¨ λ¬Έμμ κΈ°μ νλλ‘
μꡬνκ³ μλ€. κ·Έλ°λ° μμ¨ κ³μ°κ³Ό μΈμ² μΌμ μ μνκ³Ό μν μ€λΉμ μ μ©λμ§ μλλ€λ
κ²μ΄λ€. λν "μμ½νμ μν, νμ§ κ΄λ¦¬"λ νμ§ κ΄λ¦¬μ μ μ‘° μ 무μ λ 립μ μ± μμ΄λΌλ
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κ°λ κ³Ό μΆ©λλκΈ° λλ¬Έμ μμ ν΄μΌ νλ€λ μ견λ μμλ€.
The Commissioner sees no ambiguities arising from the inclusion of "testing and
quality control of drug products" in this paragraph. Indeed, comments were
received on numerous sections of the regulations (e.g., 211.2 (recodified 211.68)
and 211.25) to add the phrase after references to "manufacture, processing,
packing and holding." In all cases, the Commissioner has declined to make the
addition. The purposes of this definition are to make it clear that the phrase
"manufacture, processing, packing, or holding of a drug product" includes
operations that are commonly known by other terms such as "packaging,"
"labeling," or "quality control," and to eliminate the need for inserting references to
testing and quality control throughout the text of these regulations. Section
211.103 is modified to provide that yield determinations are not required for quality
control activities. The Commissioner believes, however, that the requirements of
211.67(b) are appropriate for quality control operations.
"μμ½νμ μν, νμ§ κ΄λ¦¬"λ‘ μΈν΄ λͺ ννμ§ μμ κ²μ΄ λ°μνλ€κ³ μκ°νμ§ μλλ€. μ¬μ€
μ¬λ¬ μΉμ (μ, 211.2(211.68λ‘ λ³κ²½), 211.25)κ³Ό κ΄λ ¨νμ¬ "μ μ‘°, κ°κ³΅, ν¬μ₯, 보κ΄"
λ€μμ μ΄ κ΅¬μ μ μΆκ°νμλ μκ²¬μ΄ λ§μ΄ μ μλμλ€. νμ§λ§ κ·Έλ κ² μΆκ°νμ§ μκΈ°λ‘
κ²°μ νλ€. μ΄ μ©μ΄ μ μμ λͺ©μ μ "μμ½νμ μ μ‘°, κ°κ³΅, ν¬μ₯ λλ 보κ΄"μ΄ "ν¬μ₯",
"λΌλ²¨λ§" λλ "νμ§ κ΄λ¦¬" κ°μ λ€λ₯Έ μ©μ΄λ‘ μλ €μ Έ μλ μμ λ ν¬ν¨νκ³ μμμ λͺ νν
νκ³ μ΄ κ·μ λ³Έλ¬Έ μ 체μ κ±Έμ³ μνκ³Ό νμ§ κ΄λ¦¬λΌλ ννμ μ½μ ν νμκ° μλλ‘ νλλ°
μλ€. μΉμ 211.103μ νμ§ κ΄λ¦¬ νλμΈ κ²½μ°μ μμ¨ κ³μ°μ΄ νμνμ§ μλλ‘ μμ νλ€.
νμ§λ§ 211.67(b)μ κΈ°μ€μ νμ§ κ΄λ¦¬ μμ μλ μ μ νλ€κ³ μκ°νλ€.
The Commissioner believes that the functions of quality control and manufacturing
can be included in the total concept of producing drug products and still be
independent. The comment did not describe how the definition would actually
cause a loss of independence of the quality control function.
νμ§ κ΄λ¦¬μ μ μ‘°λ μμ½ν μμ°μ΄λΌλ μ 체μ μΈ κ°λ μ ν¬ν¨λλ©΄μλ μ¬μ ν λ 립μ μΌ μ
μλ€. μκΈ° μ견μ μ΄ μ©μ΄ μ μκ° νμ§ κ΄λ¦¬ κΈ°λ₯μ λ 립μ±μ μ€μ λ‘ μ΄λ»κ² νΌμνλμ§
μ€λͺ νκ³ μμ§ μλ€.
76. One comment suggested that the term "warehousing" was more suitable than
the term "holding" in 210.3(b)(12).
210.3(b)(12)μμ "보κ΄(holding)"보λ€λ "warehousing"μ΄ λ μ ν©νλ€λ μκ²¬μ΄ ν 건
μμλ€.
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The Commissioner finds that, although the term "warehousing" describes the
meaning intended some of the time, the more general term "holding" is more
suitable. The Commissioner also notes that the entire phrase "manufacture,
processing, packing, or holding" is repeated from section 501(a)(2)(B) of the act.
"warehousing"λ μ΄λ μ λ μλ―Έκ° μμ§λ§, λ³΄λ€ μΌλ°μ μΈ "holding"μ΄ λ μ ν©νλ€.
λν "μ μ‘°, κ°κ³΅, ν¬μ₯ λλ 보κ΄"μ΄λΌλ μ 체 ꡬμ μ λ² μΉμ 501(a)(2)(B)μμ μΈμ©ν
κ²μ΄λ€.
77. One comment said the term "quality control" is too vague in 210.3(b)(12)
because it does not cover the responsibilities of other than the quality control
department. The comment suggested the following wording: "Manufacturing,
processing, packaging or holding of a drug product includes packaging and labeling
operations, testing and other measures taken to insure that the drug product has
the identity, strength, quality and purity which it purports to or is represented to
possess."
210.3(b)(12)μ "νμ§ κ΄λ¦¬"λ νμ§ κ΄λ¦¬ λΆμ μ΄μΈμ λ€λ₯Έ κ³³μ μ± μμ λμμΌλ‘ νμ§
μκΈ° λλ¬Έμ λ무 λͺ¨νΈνλ€λ μκ²¬μ΄ ν 건 μμλ€. λ€μκ³Ό κ°μ λ¬Έμ₯μ μ μνλ€.
"μμ½νμ μ μ‘°, κ°κ³΅, ν¬μ₯ λλ 보κ΄μ ν¬μ₯κ³Ό λΌλ²¨λ§ μμ , μν, κ·Έλ¦¬κ³ μμ½νμ΄
λͺ©νλ‘ νκ±°λ 보μ νλ κ²μΌλ‘ νμλ νμΈ, ν¨λ, νμ§, μλλ₯Ό ꡬλΉνλλ‘ λ³΄μ¦νκΈ°
μν κΈ°ν μ‘°μΉλ₯Ό ν¬ν¨νλ€."
The Commissioner does not agree that the definition is vague. The intent is to
identify several key operations that might not be perceived as an integral part of
the production of pharmaceuticals, but for purposes of CGMP regulations must be
included. It is not necessary, however, to describe every operation that is included
under the act. The responsibilities of the quality control unit are specified in
211.22 and are not affected by this definition.
μ΄ μ©μ΄ μ μκ° λͺ¨νΈνλ€λ μ견μ λμνμ§ μλλ€. μ΄ μ©μ΄ μ μμ μλλ μμ½ν μμ°μ
ν΅μ¬μ μΈ λΆλΆμΌλ‘ μΈμλμ§ μμ μ μμ§λ§ CGMP κ·μ μ λͺ©μ μ λΉμΆμ΄ λ°λμ
ν¬ν¨λμ΄μΌ νλ μ¬λ¬ μ€μ μμ μ κ·μ νλλ° μλ€. νμ§λ§ λ²μ μκ±°νμ¬ ν¬ν¨λλ λͺ¨λ
μμ μ κΈ°μ ν νμλ μλ€. νμ§ κ΄λ¦¬ μ‘°μ§μ μ± μμ 211.22μ κ·μ λμ΄ μμΌλ©°, μ΄ μ©μ΄
μ μμ μν₯μ λ°μ§ μλλ€.
78. Several comments said the definition in 210.3(b)(15) of a "quality control unit,"
taken together with its responsibilities, would mean that the quality control unit
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would duplicate functions such as engineering, which are better handled by other
professionals such as engineers. They also said the term "unit" generated
confusion vis-a-vis the "quality control department" and "quality assurance
department." Another comment said the word "perform" should be replaced with
"be responsible for."
210.3(b)(15)μ "νμ§κ΄λ¦¬μ‘°μ§(QCU)"κ³Ό μ΄ μ‘°μ§μ μ± μκ³Ό κ΄λ ¨νμ¬, μμ§λμ΄ κ°μ λ€λ₯Έ
μ λ¬Έκ°κ° λ μ μ²λ¦¬ν μ μλ μμ§λμ΄λ§ κ°μ μ 무μ νμ§κ΄λ¦¬μ‘°μ§μ μν μ΄ μ€λ³΅λλ
κ²μΌλ‘ ν΄μλ μ μλ€λ μκ²¬μ΄ λ€μ μμλ€. λν "μ‘°μ§(unit)"μ΄λΌλ ννμ "νμ§ κ΄λ¦¬
λΆμ"λ "νμ§ λ³΄μ¦ λΆμ"μ λΉκ΅ν΄ νΌλμ μ λ°νλ€κ³ νλ€. μ΄μΈμλ "μννλ€"λ₯Ό "~λ₯Ό
μ± μμ§λ€"λ‘ λ°κΎΈμ΄μΌ νλ€λ μκ²¬μ΄ μμλ€.
Functions that are properly those of the engineering department or other
specialized units because of their unique training and expertise should not be
duplicated or usurped by the quality control unit. Where expertise is in other units,
the responsibility of the quality control unit is to assure that such expertise has
been utilized. In order to make clear that quality control functions may be
performed by persons assigned to units outside the quality control unit, the
Commissioner is replacing "perform" with "be responsible for." The quality control
unit will still have the duty to assure that appropriate actions were implemented
and completed satisfactorily. The Commissioner used the word "unit" because it is
a term broadly applicable to any group within a manufacturing establishment
charged with the responsibility of quality control. The Commissioner is not
concerned about the name given by a firm to its own unit that is responsible for
quality control functions.
νΉλ³ν κ΅μ‘νλ ¨μ λ°κ³ μ λ¬Έμ±μ κ°μΆ μμ§λμ΄λ§ λΆμλ λ€λ₯Έ μ λ¬Έ μ‘°μ§μ μ 무λ₯Ό
νμ§κ΄λ¦¬μ‘°μ§μ΄ μ΄μ€μΌλ‘ νκ±°λ μΉ¨ν΄ν΄μλ μ λλ€. λ€λ₯Έ μ‘°μ§μ΄ μ λ¬Έμ±μ κ°κ³ μλ
κ²½μ°μλ κ·Έλ¬ν μ λ¬Έμ±μ λ°ννλλ‘ νλ κ²μ΄ νμ§κ΄λ¦¬μ‘°μ§μ μ± μμ΄λ€. νμ§ κ΄λ¦¬
μ 무λ₯Ό νμ§κ΄λ¦¬μ‘°μ§ μ΄μΈμ λ€λ₯Έ μ‘°μ§μ λ°°μΉλ μ¬λμ΄ μνν μλ μμμ λͺ νν νκΈ°
μνμ¬, "μννλ€"λ₯Ό "~λ₯Ό μ± μμ§λ€"λ‘ λ체νλ€. νμ§κ΄λ¦¬μ‘°μ§μ μ μ ν μ‘°μΉκ° μΆμ§λκ³
λ§μ‘±μ€λ½κ² μλ£λλλ‘ ν μλ¬΄κ° μλ€. "μ‘°μ§"μ΄λΌλ ννμ μ¬μ©ν μ΄μ λ, μ΄ μ©μ΄κ°
μ μ‘° μμ€μ κ·Έλ£Ή κ°μ΄λ° νμ§ κ΄λ¦¬ μ± μμ λΆμ¬ λ°μ μ΄λ κ·Έλ£Ήμκ²λ μ μ©λ μ μκΈ°
λλ¬Έμ΄λ€. νμ§ κ΄λ¦¬ μ 무λ₯Ό μ± μμ§λ μ‘°μ§μ νμ¬κ° μ΄λ€ λͺ μΉμΌλ‘ λΆλ₯΄κ±΄ μκ΄μλ€.
79. Several comments suggested use of the term "expected yield" instead of
"theoretical yield" in 210.3(b)(17) and in 211.192. They also suggested that the
definition include a provision for normal and expected losses.
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210.3(b)(17)κ³Ό 211.192μμ "μ΄λ‘ μμ¨" λμ "μμ μμ¨"μ΄λΌλ μ©μ΄λ₯Ό μ¬μ©νμλ
μκ²¬μ΄ λ€μ μμλ€. λν μ μ μμ€κ³Ό μμ μμ€λ ν¬ν¨μν€μκ³ μ μνλ€.
The terminology and concept of "theoretical yield" appear to be understood and
generally used in the pharmaceutical industry. The Commissioner notes that the
regulations (e.g., 211.186(b)(7) and 211.192) allow for normal and expected losses
before investigations or corrective actions are required. The concept of theoretical
yield is important as a basis upon which actual or expected yields can be compared
to the theoretical yield to aid determining acceptance.
"μ΄λ‘ μμ¨"μ΄λΌλ μ©μ΄μ κ°λ μ μ μ½μ κ³μμ μΌλ°μ μΌλ‘ μ΄ν΄λκ³ μ¬μ©λλ€κ³ μκ°νλ€.
μ΄ κ·μ (μ, 211.186(b)(7), 211.192)μ μ‘°μ¬ λλ μμ μ‘°μΉκ° νμνμ§ νλ¨ν λ,
μ μ μμ€κ³Ό μμ μμ€μ νμ©νκ³ μλ€. μ΄λ‘ μμ¨ κ°λ μ μ€μ μμ¨ λλ μμ μμ¨μ
μ΄λ‘ μμ¨κ³Ό λΉκ΅νμ¬ μ ν©νμ§ νλ¨νλλ° λμμ΄ λλ κΈ°λ³Έ ν λλ‘μ¨ μ€μνλ€.
80. One comment said the definition of "theoretical yield" is nonspecific in the
wording "quantity of components to be used." A suggested alternative wording
was "quantity of component specified by master production records for that
operation."
"μ΄λ‘ μμ¨"μ μ©μ΄ μ μμμ "μ¬μ©νλ μλ£μ μ"μ΄λΌλ ννμ νΉμ΄μ μ΄μ§ μλ€λ
μκ²¬μ΄ ν 건 μμλ€. κ·Έ λμ μ "κ·Έ μμ μ λνμ¬ λ§μ€ν° μμ° κΈ°λ‘μμ μ§μ λ μλ£μ
μ"μΌλ‘ λ°κΎΈμκ³ μ μνλ€.
The Commissioner sees no need for the suggested revision in the definition section.
The requirement for compounding in accordance with master production records is
covered elsewhere in these regulations.
κ·Έλ κ² μμ ν νμλ₯Ό λλΌμ§ λͺ»νλ€. λ§μ€ν° μμ° κΈ°λ‘μμ μκ±°ν νΌν©μ λν κΈ°μ€μ μ΄
κ·μ μ λ€λ₯Έ κ³³μμ λ€λ£¨κ³ μλ€.
81. One comment suggested insertion of the word "distinct" before the word
"stage" in paragraphs (b) (17), (18), and (19) of 210.3 because yields cannot
always be determined at any stage of manufacture. Another comment said
establishing theoretical yield is not always possible for certain processes involving
chemical reactions and production of biologicals.
210.3μ (b)(17), (18), (19)μμ "λ¨κ³(stage)" μμ "λλ ·ν(distinct)"μ΄λ ννμ
μ½μ νμλ μκ²¬μ΄ ν 건 μμλ€. μμ¨μ λͺ¨λ μ μ‘° λ¨κ³μμ νκ°ν μ μκΈ° λλ¬Έμ΄λΌλ
μ΄μ μμλ€. λν μλ¬Όνμ μ μ μ μμ°κ³Ό νν λ°μ κ΄λ ¨ μΌλΆ 곡μ μ μ΄λ‘ μμ¨μ μ ν μ
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μλ κ²½μ°λ μλ€λ μ견λ μμλ€.
The Commissioner believes that a theoretical yield can be established for all
processes. The theoretical yield for a chemical reaction, for example, would be
maximum yield obtainable under optimal reaction conditions. The Commissioner
agrees that the word "stage" may not adequately define the phase of manufacture
at which the theoretical yield should be determined. Therefore, he is adopting the
phrase "appropriate phase" in paragraphs (b) (17), (18), and (19) of 210.3.
λͺ¨λ 곡μ μ λνμ¬ μ΄λ‘ μμ¨μ μ€μ ν μ μλ€κ³ μκ°νλ€. μλ₯Ό λ€μ΄ νν λ°μμ μ΄λ‘
μμ¨μ μ΅μ λ°μ 쑰건μμ ν보 κ°λ₯ν μ΅λ μμ¨μΌ μ μλ€. "λ¨κ³(stage)"λΌλ λ¨μ΄κ°
μ΄λ‘ μμ¨μ μ ν΄μΌ ν μ μ‘° λ¨κ³λ₯Ό μ μ νκ² κ·μ νμ§ λͺ»ν μ μλ€λ μ μ λμνλ€.
κ·Έμ λ°λΌ 210.3(b)μ (17), (18), (19)μμ "μ μ λ¨κ³"λΌλ ꡬμ λ‘ λ체νλ€.
82. A number of comments have been received regarding proposed paragraphs
(b) (21), (22), (23), and (24) of 210.3. As discussed elsewhere in this preamble,
the Commissioner is not including in these regulations, at this time, specific
requirements regarding "acceptable quality level and unacceptable quality level";
therefore, definitions for these two terms are deleted from the final regulation.
Proposed paragraph (b) (21) and (24) is being retained, however, with
modifications, as 210.3(b) (20) and (21).
210.3(b)μ (21), (22), (23), (24)μ κ΄λ ¨νμ¬ λ§μ μκ²¬μ΄ μ μλμλ€. μ΄ μ λ¬Έμ λ€λ₯Έ
κ³³μμ μ€λͺ νκ³ μλ λ°μ κ°μ΄, νμ¬λ‘μ¨λ "μ ν© νμ§ μμ€κ³Ό λΆμ ν© νμ§ μμ€"κ³Ό
κ΄λ ¨νμ¬ κ΅¬μ²΄μ μΈ κΈ°μ€μ μ΄ κ·μ μ ν¬ν¨ν μκ°μ μλ€. κ·Έλ¬λ―λ‘ μ΄ λ μ©μ΄μ μ μλ
μ΅μ’ κ·μ μμ μμ νλ€. νμ§λ§ κ·μ μμ (b)(21)κ³Ό (24)λ μμ μ κ±°μ³ 210.3(b)(20)κ³Ό
(21)λ‘ νλ€.
83. One comment suggested including in the proposed definition of "acceptance
criteria" (proposed 210.3(b)(21)) the sentence: "Such acceptance criteria may be
altered if evidence demonstrates that a valid reason exists for establishing revised
acceptance criteria following an appropriate documented quality assurance
conference."
"νμ© κΈ°μ€"(κ·μ μ 210.3(b)(21))μ μ©μ΄ μ μμ λ€μ λ¬Έμ₯μ ν¬ν¨μν€μλ μκ²¬μ΄ ν 건
μμλ€. "μ μ ν νμ§ λ³΄μ¦ νμλ₯Ό μ€μνκ³ λ¬Έμνλ₯Ό ν λ€μμ νμ© κΈ°μ€μ μμ ν
μ ν¨ν μ΄μ κ° μ‘΄μ¬ν¨μ μ¦λͺ νλ μ¦κ±°κ° μμΌλ©΄, νμ©κΈ°μ€μ μμ ν μ μλ€."
The Commissioner notes that the proposed definition, now 210.3(b)(20), would not
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preclude a change in product specifications or acceptance criteria if such change is
appropriate. There is no need to incorporate the proposed language.
νμ¬λ 210.3(b)(20)μΈ μ΄ μ©μ΄ μ μλ μ μ ν κ²½μ°μ μ ν κ·κ²©μ΄λ νμ© κΈ°μ€μ λ³κ²½μ
λ°°μ νκ³ μμ§ μλ€. μκΈ° μ견μ λ¬Έμ₯μ ν¬ν¨μν¬ νμκ° μλ€.
84. One comment suggested elimination of the word "reject" from proposed
210.3(b)(21), stating that material which is not accepted may be reworked or
returned to the supplier.
210.3(b)(21)μμ "λΆμ ν©(reject)"μ΄λΌλ λ¨μ΄λ₯Ό μμ νμλ μκ²¬μ΄ μμλλ°, μμ©
λΆκ°λ₯ν λ¬Όνμ μ¬κ°κ³΅νκ±°λ 곡κΈμ 체μκ² λ°νν μ μκΈ° λλ¬Έμ΄λΌλ κ²μ΄λ€.
The Commissioner does not agree with this suggestion. The term "reject" does not
denote the ultimate disposition of the product, only that it is not acceptable for use
as is.
μ΄ μ견μ λμνμ§ μλλ€. "λΆμ ν©"μ΄λ ννμ κ·Έ μ νμ κΆκ·Ήμ μΈ μ²λ¦¬μ κ΄ν κ²μ΄
μλλΌ, λ¨μ§ κ·Έ μ νμ΄ κ·Έ μνλ‘λ μ¬μ©μ μ ν©νμ§ μλ€λ μλ―Έμ΄λ€.
85. One comment suggested that "sampling plans," referred to in proposed
210.3(b)(21), are not the only technique used to form a basis for acceptance and
rejection.
κ·μ μ 210.3(b)(21)μ "κ²μ²΄ μ±μ·¨ κ³ν"μ μ /λΆ νμ μ κ·Όκ±°κ° λλ μ μΌν κΈ°λ²μ΄
μλλΌλ μκ²¬μ΄ ν 건 μμλ€.
The Commissioner has used the term "sampling plan" in a broad context here. The
term can mean both a plan for collection of physical units for testing, or it can
mean a schedule by which an examination of some sort is done.
μ¬κΈ°μ "κ²μ²΄ μ±μ·¨ κ³ν"μ΄λΌλ μ©μ΄λ λμ μλ―Έλ‘ μ¬μ©λλ€. μ΄ μ©μ΄λ μνμ μ¬μ©ν
물리μ λ¬Όνμ μμ§μ μν κ³νμΌ μλ μκ³ , μλλ©΄ μ΄λ€ μ’ λ₯μ κ²μ¬λ₯Ό μ€μνκΈ° μν
μΌμ μ μλ―ΈνκΈ°λ νλ€.
86. Numerous comments said the term "at random" should be deleted from
proposed 210.3(b)(24). Among the reasons given were that "random" has a
limited meaning in statistics, that some samples are best taken on a stratified basis,
such as right after each start-up of a run, and that some samples are taken on a
timed basis.
κ·μ μ 210.3(b)(24)μμ "무μμ"λ₯Ό μμ ν΄μΌ νλ€λ μκ²¬μ΄ λ§μλ€. "무μμ"λ
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ν΅κ³νμ μΈ μλ―Έκ° λ³λ‘ μμΌλ©°, μΌλΆ κ²μ²΄λ κ³μΈ΅ν λ°©μμΌλ‘ μ·¨νλ κ²μ΄ κ°μ₯ μ’κ³ (μ,
μμ μμ μ§ν), μ΄λ€ κ²μ²΄λ μκ°μ μ ν΄ λκ³ μ±μ·¨νκΈ°λ νκΈ° λλ¬Έμ΄λΌλ μ΄μ μμλ€.
The Commissioner is persuaded that the term "at random" without additional
clarification may be too limiting for this definition and modifies the final regulation
accordingly.
μΆκ°μ μΌλ‘ λͺ ννκ² μ€λͺ νμ§ μκ³ "무μμλ‘"λΌλ ννμ μ¬μ©νλ©΄ μ§λμΉκ² μ νμ μΈ
μλ―Έκ° λ μ μλ€λ μ μ λμνμ¬, κ·Έμ λ°λΌ μ΅μ’ κ·μ μμλ μ©μ΄ μ μλ₯Ό μμ νλ€.
87. In reviewing the proposed regulations, the Commissioner concludes that 211.2
and 211.68 should be combined into a new 211.68. Proposed 211.2 is deleted,
and the substance of the requirements is included in the new 211.68. The
comments relating to 211.2 are discussed with those for 211.68.
κ·μ μμ κ²ν νλ κ³Όμ μμ 211.2μ 211.68μ ν΅ν©νμ¬ μλ‘μ΄ 211.68λ‘ λ§λ€ νμκ°
μλ€λ κ²°λ‘ μ λ΄λ Έλ€. κ·μ μμ 211.2λ₯Ό μμ νκ³ , κ·Έ κΈ°μ€ μμλ€μ μλ‘μ΄ 211.68μ
ν¬ν¨μν¨λ€. 211.2μ κ΄λ ¨λ μ견λ€μ 211.68μμ μ€λͺ νλ€.
88. Three comments were received regarding proposed 211.3 on definitions for Part
211. Two comments said the section is duplicative and should be deleted. The
other comment noted that some of the words defined in referenced 210.3 are not
used in Part 211.
ννΈ 211μ μ©μ΄μ μμ κ΄ν 211.3κ³Ό κ΄λ ¨νμ¬ 3건μ μκ²¬μ΄ μ μλμλ€. 2건μ μ΄
μΉμ μ΄ μ€λ³΅λλ―λ‘ μμ ν΄μΌ νλ€λ κ²μ΄μλ€. λ€λ₯Έ μ견μ 210.3μ μΌλΆ μ©μ΄λ ννΈ
211μμ μ¬μ©λμ§ μλλ€λ κ²μ΄μλ€.
The Commissioner finds that the reference to 210.3 that appears in 211.3 is
valuable as a cross reference. In addition, he anticipates a need for a definition
section in each part of the CGMP regulations to accommodate terms specific to that
individual part but not others. This scheme has already been used in the proposed
CGMP regulations for Part 212 relating to large volume parenteral (LVP) drug
products, published in the FEDERAL REGISTER of June 1, 1976 (41 FR 22202).
The Commissioner sees no inconsistency in that terms defined in 210.3 may not be
used in Part 211, because they may be used in other parts (e.g., Parts 225 and
226). The definitions apply only where the term is used.
211.3μμ 210.3μ μΈμ©ν κ²μ μνΈ μ°Έμ‘°λ‘ κ°μΉκ° μλ€. μ΄μΈμλ CGMP κ·μ μ κ°
ννΈμ μ©μ΄ μ μ μΉμ μ λμ΄, κ·Έ ννΈμλ§ ν΄λΉλλ μ©μ΄λ₯Ό μ 리ν νμκ° μλ€κ³ λ³Έλ€.
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μ΄ λ°©μμ μ΄λ―Έ 1976λ 6μ 1μΌμ μ°λ°©κ΄λ³΄(41 FR 22202)μ κ²μ¬λ LVP(large volume
parenteral) μμ½ν κ΄λ ¨ ννΈ 212 CGMP κ·μ μμ μ±νλμλ€. 210.3μ κ·μ λ μ©μ΄κ°
ννΈ 211μμ μ¬μ©λμ§ μλλ€κ³ ν΄μ μΌκ΄μ±μ΄ μλ€κ³ λ³΄μ§ μλλ€. λ€λ₯Έ ννΈ(μ, ννΈ
225 λ° 226)μμ μ¬μ©λ μ μκΈ° λλ¬Έμ΄λ€. μ©μ΄ μ μλ κ·Έ μ©μ΄κ° μ¬μ©λλ κ³³μμλ§
μ μ©λλ€.