中英文-FDA Regulatory Affairs1.1

FDA Regulatory Affairs: A Guide for Prescription

Drugs

目录

1< /p>

、药品发展和

FDA

概述

1

、

Overview

of

Drug

Development

and

the FDA

——

Douglas J. Pisano

药品发展和

F DA

概述

1.1

Brief

History

of

Drug

Laws

and

1.1

药品法律和监管历史简述

Regulations

Prior to 1902, the U.S. government took a

在

1902

年之前，美国政府没有 对药品进

hands-off approach to the regulation of drugs.

行监管。

当时市面上的绝大多数药品都所谓

Many

of

the

drugs

available

were

so-called

的“专利药物”

，因为它们或多或少都是这样

“patent

medicines”

which

were

so

named

宣传的。

即使美国药典（

）在

1820

年成

because each had a more or less descriptive or

为美国的第一份官方简编，美国的法律法规

patent

name.

No

laws,

regulations

or

或标准仍就一片空白。美国药典为医生和药

standards

existed

to

any

noticeable

extent

剂师提供了剂量和纯度的标准。

even

though

the

United

States

Pharmacopeia

(USP)

became

a

reality

in

1820

as

the

first

official

compendium

of

the

U.S.

The

USP

set

standards for strength and purity that could be

used

by

physicians

and

pharmacists

who

needed

centralized

guidelines

to

extract,

compound,

and

otherwise

utilize

drug

components that existed at the time.

However, in 1848, the first American drug

然而，

1848

年，第一个 美国药品法“药

law,

the

Drug

Importation

Act,

was

enacted

品进口法”颁布。背景是当时正在墨西哥服

when

American

troops

serving

in

Mexico

役的美国军队遭受严重传染，而此时抗疟疾

became

seriously

affected

when

adulterated

药物奎宁被发现是掺假药。这项法律要求对

quinine, an antimalarial drug, was discovered.

实验室进行检查，拘留，甚至销毁不符合法

This

law

required

laboratory

inspection,

定标准的药品。

后来，在

年，为响应

detention, and even destruction of drugs that

于由密苏里州圣路易斯的小实验室制造的用

did

not

meet

acceptable

standards.

Later,

in

于破伤风感染的白喉抗毒素，通过了病毒，

1902,

the

Virus,

Serum

and

Toxins

Act

血清和毒素法（

Biologics Control Act

）

。

背景

(Biologics Control Act) was passed in response

是

13

名小学生由于接种受污染的血清而死

to

tetanusinfected

diphtheria

antitoxin

which

亡。

当时尚无针对血液制品的纯度或效力的

was manufactured by a small laboratory in St.

国家标准。此项法律授权公共卫生服务部对

Louis,

MO.

Thirteen

school

children

died

as

a

用于预防或治疗疾病的血清、疫苗和相关生

result

of

the

tainted

serum.

No

national

物制品的州际销售进行许可管理和监督管

standards

were

as

yet

in

place

for

purity

or

理。

potency. The Act authorized the Public Health

Service

to

license

and

regulate

the

interstate

sale

of

sera,

vaccines,

and

related

biologic

products used to prevent or treat disease.

This Act also spurred Dr. Harvey W. Wiley,

chief

chemist

for

the

Bureau

of

Chemistry,

a

branch

of

the

U.S.

Department

of

Agriculture

(US

DA)

and

the

forerunner

for

today’s

U.S.

Food

and

Drug

Administration

(FDA),

to

investigate

the

country’s

foods

and

drugs.

He

established

the

Hygienic

Table,

a

group

of

young

men

who

volunteered

to

serve

as

human

guinea

pigs,

and

who

would

allow

Dr.

Wiley

to

feed

them

a

controlled

diet

laced

with

a

variety

of

preservatives

and

artificial

colors.

More

popularly

known

as

the

“Poison

Squad,”

they

helped

Dr.

Wiley

gather

enough

data

to

prove

that

many

of

America’s

foods

and

drugs

were

adulterated,

the

products’

strength or purity was suspect or misbranded,

or

products

had

inadequate

or

inaccurate

labeling.

Dr.

Wiley’s

efforts,

along

with

publication

of

Upton

Sinclair’s

The

Jungle

(a

book

revealing

the

putrid

conditions

in

America’s

meat

industry),

were

rewarded

w

hen Congress passed America’s first food and

drug law in 1906, the Pure Food and Drug Act

(USPFDA,

also

known

as

the

Wiley

Act).

The

Wiley

Act

prohibited

interstate

commerce

of

misbranded

foods

or

drugs

based

on

their

labeling. It did not affect unsafe drugs in that

its

legal

authority

would

come

to

bear

only

when

a

product’s

ingredients

were

falsely

labeled.

Even

intentionally

false

therapeutic

claims were not prohibited.

This

began

to

change

in

1911

with

the

enactment

of

the

Sherley

Amendment

which

intended

to

prohibit

the

labeling

of

medications with false therapeutic claims that

were intended to defraud the purchaser. These

amendments,

however,

required

the

government

to

find

proof

of

intentional

labeling fraud. Later, in 1937, a sentinel event

occurred

that

changed

the

entire

regulatory

picture. Sulfa became the miracle drug of the

该法案还引发了时任美国农业部

（< /p>

USDA

）

分支机构化学局首席化学家< /p>

Harvey

W.

Wiley

博士的关注。

FDA

的前身就是美国农业部< /p>

（

USDA

）分支机构化学局。

他建立了卫生研究计划，招募了一群年

轻男性 志愿者，

同意参加

Wiley

博士对防 腐剂

和人工色素的试验研究。这就是后来著名的

“毒药队”

，是他们帮助了

Wiley

博士收集了

足够的实验数据，证明了美国的许多食品和

药物掺假，产品的剂量或纯度是可疑的或与

标签不符，或产品标识信息不足或不准确。

Wiley

博士后来写了

Upton Sinclair's The Jungle

（一本揭示美国肉业肮脏条件的书）

。

1906

年

在国 会通过美国第一个食品和药物法，纯净

食品和药物法案（

USP FDA

，称为

Wiley Act

）< /p>

上，

Wiley

博士被嘉奖。

Wiley

法案禁止不符

合标识信息的错误标签食品或药物在州际间

贸易销售。它不影响不安全的药物，因为其

法律权威只有在产品的成分被错误地贴上标

签时才会发生。即使 故意的虚假治疗信息也

没有被禁止。

这在

19 11

年随着“谢利修正案”的颁布

而开始改变，该修订旨在禁止 不符合用药标

识信息的虚假治疗信息，而达到欺骗购买者

的目的 。

然而，修正案要求政府找到有意标

签欺诈的证据。

后来，在

1937< /p>

年，发生了

一个警示事件，彻底颠覆了美国药品监管。

磺胺类药成为当时的奇迹药物，被用于治疗

许多 危及生命的感染。

但它口感不好，难吞

咽，这导致制药者需要去寻求一个解决方案。

time

and

was

used

to

treat

many

life-threatening

infections.

It

tasted

bad

and

was hard to swallow which led entrepreneurs

to seek a palatable solution. S.E. Massingill Co.

of

Bristol,

TN,

developed

what

the

company

thought

was

a

palatable,

raspberry

favored

liquid product. However, they used diethylene

glycol to solubilize the sulfa. A volume of 6 gal

of

this

dangerous

mixture,

Elixir

of

Sulfanilamide,

killed

107

people,

mostly

children.

The result was the passage of one of the

most comprehensive statutes in the history of

American health law. The Federal Food, Drug,

and Cosmetic Act of 1938 (FDCA) repealed the

Sherley

Amendments

and

required

that

all

new

drugs

be

tested

by

their

manufacturers

for safety and that those tests be submitted to

the government for marketing approval via the

New

Drug

Application.

The

FDCA

also

mandated

that

drugs

be

labeled

with

adequate

directions

if

they

were

shown

to

have

had

harmful

effects.

In

addition,

the

FDCA

authorized

the

FDA

to

conduct

unannounced

inspections

of

drug

manufacturing

facilities.

Though

amended

many

times

since

1938,

the

FDCA

is

still

the

broad

foundation

for

statutory

authority

for

the FDA as it exists today.

However,

a

new

crisis

loomed.

Throughout

the

late

1950s,

European

and

Canadian

physicians

began

to

encounter

a

number

of

infants

born

with

a

curious

birth

defect

called

phocomelia,

a

defect

that

resulted in limbs resembling flippers similar to

those found on seals. These birth defects were

traced

back

to

mothers

who

had

been

prescribed the drug thalidomide in an effort to

relieve

morning

sickness

while

pregnant.

The

anufacturer

of

this

drug

applied

for

U.S.

marketing approval of the drug as a sleep aid.

However,

due

to

the

efforts

of

Dr.

Frances

O.

Kelsey, FDA’s chief medical officer at the time,

the case was made that the drug was not safe,

S.E.

Massingill

C o.

，

Bristol

，

TN

，开发了该公

司认为是一种树莓味的爽口液体产 品。

然

而，他们使用二甘醇溶解磺胺。

< /p>

6

加仑的这

种危险混合物磺胺药，杀死< /p>

107

人，大多还

是儿童。

结果是 通过了美国健康法历史上最全面

的法规。

1938

年的《联邦食品，药品和化妆

品法案

（

FDCA

）

》