Download Introduction to Drugs and Pharmacy

New Drug Development
and Approval Process
Contents
1.
2.
3.
4.
Drug discovery and drug design
Biological characterization
Early formulation studies
The investigational New Drug (IND)
Application(研究性新药申请）
5. The New Drug Application (NDA)
The Federal Food, Drug, and Cosmetic
Act,as regulated through Title 21 of
the U.S. Code of Federal Regulations,
requires a new drug to be approved by the
Food and Drug Administration(FDA) before
it may be legally introduced in interstate
commerce
To gain approval for marketing, a drug’s
sponsor (e.g., a pharmaceutical company) must
demonstrate, through supporting scientific
evidence, that the new drug or drug product
is safe and effective for its proposed use.
The sponsor must also demonstrate that the
various processes and controls used in
producing the drug substance and in
manufacturing, packaging, and labeling are
properly controlled and validated to ensure
that the product meets established standards
The process and time course from drug discovery to
approval for marketing can be divided into following
process:
New Chemical Entity (synthesis)
Prefomulation studies-define the physical and chemical
properties
Formulation studies-develop the initial features of the
proposed pharmaceutical product or dosage form
Investigational new drug application(IND)-for initial
testing in humans
Preclinical and Clinical studies
Phase I-initial testing in humans
Phase II, Phase III -progressive humanTrials
New drug application (NDA)-seeking approval
to market the new product.
Content of a product’s approved labeling-essential
chemistry, pharmacology, toxicology, indications
and contraindication for use, adverse effects,
formulation composition, dosage, and storage
requirements.
Treatment IND, Orphan drug
Supplemental new drug application (SNDA)
Abbreviated new drug application(简化新药申请) to
gain approved to market a duplicate
Antibiotic drug; biologics; Medical devices
1. Drug Discovery and Drug
Design
1)
2)
3)
4)
5)
Sources of new drugs
A goal drug
Methods of drug discovery
A lead compound
Prodrugs
1) Sources of new drugs
• New drugs may be discovered from a
variety of natural sources or synthesized
in the laboratory.
• Plant materials have served as a reservoir
of potential new drugs.
• Reserpine （利血平）, a tranquilizer
（镇定剂） and hypotensive agent,
from the folklore remedy Rauwolfia
serpentina（萝芙木属蛇根碱）.
• Periwinkle（长春花）, or Vinca rosea,
in the treatment of diabetes
mellitus.
• Vinblastine （长春碱） and vincristine
（ 长 春 新 碱 ） , from Vinca rosea,
exhibited antitumor capabilities.
• Paclitaxel (Taxol), from an extract of
the Pacific yew （紫杉）tree, is used
in the treatment of ovarian cancer.
• After the isolation and structural identification
of active plant constituents, organic chemists
may recreate them by total synthesis in the
laboratory.
• The natural chemical could be also used as the
starting material in the creation of slightly
different
chemical
structures
through
molecular manipulation. The new structures,
termed semisynthetic drugs.
• Animals have served humans in their
search for drugs in a number of ways.
• Hormonal substances, such as thyroid
（ 甲 状 腺 ） extract, insulin, and
pituitary （ 脑 垂 体 ） hormone obtained
from the endocrine glands of cattle,
sheep, and swine.
• The use of animals in the production of
various biologic products, including
serums, antitoxins, and vaccines.
• New vaccines for diseases as AIDS and
cancer are being developed through the
use of cell and tissue cultures.
• A new era in the development of
pharmaceutical products comes forth as
a result of the advent of genetic
engineering, the manipulation of the
double helix, the spiral DNA chain of life.
（药物产品发展的新时代到来由于基因工
程，生命DNA链的双螺旋操作的出现。）
• Through this process, will come more
abundant and vastly purer antibiotics,
vaccines, and yet unknown chemical and
biological products to combat human
disease.
• 通过这些过程，将会出现丰富而大量的
更纯的抗生素、疫苗、还有其他未知的
化学和生物制品，以抵抗人类疾病。
There are two basic technologies that
drive the genetic field of drug
development
• Recombinant DNA (rDNA)
• Monoclonal antibody (MoAB)
production
2) A goal drug （目标药物）
In theory, a “goal drug”
• would produce the specifically desired effect,
• be administered by the most desired route
(generally orally) at minimal dosage and
dosing frequency,
• have optimal onset and duration of activity,
理论上，目标药物应能通过最理想的途径
（通常为口服）以最小的剂量和给药频率
给药，能产生特异的期望疗效，具有最理
想的起效和持续时间，
• exhibit no side effects,
• following its desired effect would be eliminated
from the body efficiently, completely, and without
residual effect.
• it would be easily produced at low cost,
• be pharmaceutically elegant,
• physically and chemically stable under various
conditions of use and storage.
（无副作用，并在发挥疗效后能完全有效地从体内消
除，且无残留效应。它应该易于生产，费用低，制
剂产品美观，在不同的使用和贮藏条件下物理和化
学上稳定。）
3) Methods of drug discovery
• Most drugs are the result of carefully
designed research programs of screening,
molecular modification, and mechanismbased drug design.
（大多数药物是精心设计的研究过程的结果，包
括：筛选、分子修饰和基于机制的药物设计。）
• To detect and evaluate biological activity,
bioassays are used to differentiate the
effect and potency of the test agent
compared with controls of known action
and effect.
In vitro
Cell culture
In vivo
Disease-specific
Animal models
• New methods, as high throughput
screening, are capable of examining
15000 chemical compounds a week using
10-20 biological assays.
• High-throughput screening (HTS) is a
method for scientific experimentation
especially used in drug discovery and
relevant to the fields of biology and
chemistry.
• To be effective, this requires a sizeable
and chemically diverse collection of
compounds to examine, which many
pharmaceutical and chemical companies
have in “chemical libraries.”
（为了有效地利用它，这需要有相当大量
的不同化学物质来测试，通常许多制药
公司或化学品公司有“化合物库”）
• Molecular modification involves the
chemical alteration of a known and
previously
characterized
organic
compound for the purpose of enhancing
its usefulness as a drug.
（分子修饰涉及化学改变已知和特性明了
的有机化合物以改善其作为药物的有效
性。）
Aims for molecular modification
• Enhancing its specificity for a particular body
target site;
• Increasing its potency;
• Improving its rate and extent of absorption;
• Modifying to advantage its time-course in the
body;
• Reducing its toxicity;
• Changing its physical or chemical properties to
provide pharmaceutically desired features;
How?
Changes in
• functional groups
• Ring structures
• Configuration （构型）
（ＳＡＲ）
• Mechanism-based drug design involves
molecular modification in designing a drug
that interferes specifically with the known
or suspected biochemical pathway or
mechanism of a disease process.
（基于机制的药物设计包括通过分子修饰设
计药物，这种药物能够特异性地影响疾病
过程的已知或可能的生化途径或机制。）
The intention is the interaction of the drug with
• specific cell receptors,
• enzyme systems,
• the metabolic processes of pathogens or tumor
cells,
resulting in a blocking, disruption, or reversal
of the disease process.
（设计的意图是影响药物与特异性受体、酶系统、
病原体或癌细胞的代谢途径的相互作用，导致
疾病过程的阻滞、破坏或逆转。）
Molecular graphics, the use of computer
graphics to represent and manipulate the
structure of the drug molecule to “fit” the
simulated molecular structure of the
receptor site.
（利用计算机绘图来描绘和操纵药物分子的
结构使之“适合”于受体部位的分子设计是
药物分子设计的有用的和互补的工具。）
• Enalaprilat(依那普利拉，Vasotec)inhibits the angiotensin-converting
enzyme
• Ranitidine (Zantac)-an inhibitor of
histamine at the H2-receptor
• Sertraline (舍曲林, Zoloft)-inhibits
the central nervous system neuronal
uptake of serotonin（5-羟色胺 ）
4) A Lead Compound（先导化合物）
• is a prototype （ 原 形 化 学 物 质 ）
chemical compound that has a
fundamental
desired
biologic
or
pharmacologic activity.
（先导化合物是一种具有生物学和药理学活
性基本要求的原型化学物质。）
• Although active, the lead compound
may not posses all of the features
desired; i.e., potency （ 效 力 ） ,
absorbability （ 吸 收 性 ） , solubility,
low toxicity, and so forth.
• The medicinal chemist may seek to
modify the lead compound’s chemical
structure to achieve the desired
features while reducing the undesired
one.
• Finasteride (非那雄胺, Proscar) –
benign prostatic hyperplasia
• Propecia (a lower recommended
dosage)-male pattern baldness.
5) Prodrugs
• is a term used to describe a compound
that
requires
metabolic
biotransformation after administration
to
produce
the
desired
pharmacologically active compound.
(前体药物使之能够在给药后经体内代谢性
生物转化成具有期望的药理活性化合物的
化合物。）
• The conversion of an inactive prodrug to
an active compound occurs primarily
through enzymatic biochemical cleavage.
• Prodrugs may be designed preferentially
for the following reasons.
• Solubility
• Absorption
• Biostability
• Prolonged release
• FDA’s definition of a new drug
• According to the FDA, a new drug is any that is not
recognized as being safe and effective in the conditions
recommended for its use among experts who are qualified
by scientific training and experience.
• A change in a previously approved drug product’s
formulation or method of manufacture constitutes newness
under the law
• A combination of two or more old drugs or a change in
usual proportions of drugs in an established ones
• A proposed new use for an established drug, a new dosage
schedule or regimen, a new route of administration, or a
new dosage form all cause a drug or drug product’s status
to new and triggers reconsideration for safety and efficacy
• Drug Nomenclature
• 系统命名法
2. Biological characterization
1) Pharmacology
2) Drug metabolism
3) Toxicology
Prospective drug substances must
undergo preclinical testing for biologic
activity to assess their potential as
useful therapeutic agents.
pharmacology
Drug metabolism
toxicology
1) Pharmacology
• embraces the physical and chemical
properties,
• biochemical and physiological effects
• mechanisms of action, absorption,
distribution, biotransformation,
excretion,
• useful applications of drugs.
• Pharmacodynamics is the study of the
biochemical and physiological effects of
drugs and their mechanisms of action.
• Pharmacokinetics deals with the
absorption, distribution, metabolism or
biotransformation, and excretion of
drugs.
• Clinical pharmacology applies
pharmacologic principles to the study of
the effects and actions of drugs in humans.
Most diseases arise from
• a biochemical imbalance
• An abnormal proliferation of cells
• An endogenous deficiency
• An exogenous chemical toxin
• Invasive pathogen (病原体)
• Intricate enzymatic reactions
• Structure-activity relationships
(SAR)
• Relationship between the quantity of
drug molecules available for
interaction and the capacity of the
specific receptor site
• Certain cells within the body are
capable of binding drugs without
eliciting a drug effect.
Cell culture
Isolated animal tissues
Whole animal studies
Animal models of human disease
The primary objective of the animal
studies is
• to obtain basic information on the drug’s
effects that may be used to predict safe
and effective use in humans.
2) Drug Metabolism
A series of animal studies of a proposed
drug’s metabolism are undertaken to
determine:
• the rate, primary and secondary sites,
and mechanism of the drug’s metabolism
in the body,
• the chemistry and pharmacology of any
metabolites.
• Drugs that enter the hepatic( 肝 脏 的 )
circulation after absorption from the gut,
as after oral administration, are
particularly exposed to rapid drug
metabolism.
• This transit through the liver and
exposure to the hepatic enzyme system is
termed the first-pass effect.
• Drug metabolism or biotransformation
frequently results in the production of one
or more metabolites of the administered
drug, some of which may be
pharmacologically active compounds.
• When metabolites are found, they are
chemically and biologically characterized
for activity and toxicity.
3) Toxicology is the area of pharmacology that
deals with the adverse, or undesired, effects
of drugs.
• In drug development programs, preclinical
drug safety evaluation or toxicity studies are
undertaken to determine:
- The substance’s potential for toxicity with
short-term (acute effects) or long-term use
(chronic effects).
- the substance’s potential for specific organ
toxicity,
- the mode, site, and degree of toxicity,
- dose-response relationships, for low-highand intermediate doses over a specified
time course,
- gender, reproductive, or teratogenic (产生
畸形的) toxicities,
- the substance’s carcinogenic and genotoxic
(遗传毒性的)potential.
① Acute or short-term toxicity studies
These studies are designed to determine
• the toxic effects of a test compound
• when administered in a single dose and/or
in multiple doses
• over a short period, usually a single day.
•
•
•
•
•
The test compound is administered at
various dose levels, with toxic signs
observed for
onset （观察毒性反应的开始）
progression or reversal （发展或逆转）
severity （严重性）
mortality （死亡率）
rates of incidence （事件的发生率）
•
•
•
•
•
The animals are observed and
compared with controls for
eating and drinking habits,
weight change,
toxic effects,
psychomotor changes（精神变化）,
any other signs of untoward effects,
usually over a 30 day postdose period.
② Subacute（亚急性） or subchronic
（亚慢性）studies
• Animal toxicity studies of a minimum of 2
weeks duration of daily drug administration
at three or more dosage levels to two animal
species are required to support the initial
administration of a single dose in human
clinical testing.
• These studies are termed subacute or
subchronic.
Chronic toxicity studies,
For drugs intended to be given to
humans for a week or more, animal
studies of 90 to 180 days in length
must demonstrate safety.
③ Carcinogenicity studies （致癌性研究）
Carcinogenicity testing is usually a
component of chronic testing，is
undertaken when the compound has
shown sufficient promise as a drug to
enter human clinical trials.
• Carcinogenicity studies are usually
carried out in a limited number of rat
and mouse strains for which there is
reasonable information on
spontaneous tumor incidence（自发性
肿瘤形成）.
④ Reproduction studies （生殖研究）
• These studies are undertaken to reveal any
effect of an active ingredient on mammalian
reproduction. Included in these studies are
• fertility and mating behavior (抚养和交配行
为）
• Early embryonic and pre- and post-natal
development （胚胎早期、早产和产后发育）
• Multigenerational effects （多代影响）
• Teratology （致畸性）
3. Early formulation studies
1) Preformulation studies
2) Initial product formulation and clinical
trial materials
Physical
chemical
properties
from initial
to final
formulation
Clinical
trials
from pilot
plant to
scale-up
large
scale
manufacturing
1) Preformulation studies （处方前研究）
Each drug substance has intrinsic （固有的）
chemical and physical characteristics that
must be considered before the development
of a pharmaceutical formulation
① Drug solubility
• A drug substance administered by any
route must possess some aqueous
solubility for systemic absorption and
therapeutic response.
• Poorly soluble compounds (less than
10mg/ml) may exhibit either incomplete or
erratic（不稳定） absorption and thus
produce a minimal response at desired
dosage.
Enhanced aqueous solubility may be
achieved by
• preparing more soluble derivatives of the
parent compound, such as salts or esters;
• by chemical complexation;
• by reducing the drug’s particle size.
② Partition coefficient
To produce a pharmacologic response, a
drug molecule must first cross a biologic
membrane of protein and lipid, which
acts as a lipophilic barrier to many drugs.
A drug’s partition coefficient is
• a measure of its distribution in a
lipophilic/hydrophilic phase system,
• indicative of its ability to penetrate
biologic multiphase systems.
（二）分配系数
• 油/水分配系数是分子亲脂特性的度量，
在药剂学研究中主要用于预见药物对在
体组织的渗透或吸收难易程度。
• 分配系数（partition coefficient，P）
代表药物分配在油相和水相中的比例。
在油相中药物的质量浓度
P=
在水相中药物的质量浓度
③ Dissolution rate
• The rate at which a drug substance
dissolves in a medium is called its
dissolution rate.
• Dissolution rate data, when considered
along with data on a drug’s solubility,
dissolution constant, and partition
coefficient, can provide an indication of
the drug’s absorption potential following
administration.
• For a chemical entity, its acid, base,
or salt forms, as well as its physical
form (e.g. particle size), may result in
substantial differences in the
dissolution rate.
④ Physical form
The crystal or amorphous forms and
particle size of a powdered drug can
affect the dissolution rate, and thus
the rate and extent of absorption, for
a number of drugs.
⑤ Stability
The chemical and physical stability of
a drug substance alone, and when
combined with formulation components,
is critical in preparing a successful
pharmaceutical product.
2) initial product formulation and clinical
trial materials
An initial product is formulated
- using the information gained during the
preformulation studies
- with consideration of the doses, dosage
form, route of administration desired
for the clinical studies and for the
proposed marketed product.
• For phase 1 studies, orally administered
drugs, capsules are employed containing
the active ingredient alone, without
pharmaceutical excipients.
• Excipients are included in the formulation
for Phase 2 trials.
• Different formulations may be prepared
and examined to develop the one having
the desired characteristics.
• During phase 2, the final dosage form is
selected and developed for Phase 3 trials.
药物制剂处方设计前工作
一、任务和要求
• 一个药物从合成到最后上市，大致经历：
①药理活性的筛选；②初步药理学及分析
方法研究；③处方前工作；④临床研究;
⑤处方与制备工艺研究； ⑥ 制剂药理、
毒理研究；⑦申报工作。
• 其中处方前工作在整个研制过程中占有重
要地位。
处方前工作的主要任务：
• 处方前工作将为该药物制剂的开发提供
决定性的参考价值：
①获取新药的相关理化参数；
②测定其动力学特征；
③测定与处方有关的物理性质；
④测定新药物与普通辅料间的相互作用。
二、文献检索
• 1、光盘检索：CA、IPA、Medline、Drug &
Pharmacology、中国生物医学文献光盘数据库、中国
科技期刊光盘数据库等。
• 2、网络检索：Medline、Rxlist、griffin、pharmacy、
US patent、FDA、中国生物科技期刊库、万方数据库、
CPA等
• 3、期刊检索：J Pharm Sci, Pharm Res, DDIP, J Contr
Rel, Int J Pharm,
IPA, CA, 中国药学文摘、国内药学期刊杂志等。
• 4、书刊检索：
• 5、工具书检索：USP、BP、CP、PDR、Mardindale、
Pharm Project等。
• 6、专利检索：
• The Investigational New Drug (IND)
Application
• Under the Food, Drug, and Cosmetic Act as
amended, the sponsor of a new drug is required
to file with the FDA an IND before the drug
may be given to human subjects.
• This is to protect the rights and safety of the
subjects and to ensure that the investigational
plan is sound and is designed to achieve the
stated objectives
• After submission of the IND, the sponsor must
delay use of the drug in human subjects for not
less than 30 days from the date the FDA
acknowledge receipt of the application.
•
•
•
•
(1) Content of the IND
(2) The Clinical Protocol
(3) Pre-IND Meetings
On request, the FDA will advise a sponsor on
scientific, technical, or formatting concerns
relating to the preparation and submission of an
IND
• (4) FDA Review of an IND Application
• The FDA’s objectives in reviewing an IND are to
protect the safety and rights of the human
subjects and to help ensure that the study allows
the evaluation of the drug’s safety and
effectiveness.
• (5) FDA Drug Classification system
• Upon receipt and examination of an IND or
NDA, the FDA classifies the drug by chemical
type and therapeutic potential. Page 49
• (6) Phases of a Clinical Investigation
• An IND may be submitted for one or more
phases of a clinical investigation,namely Phase 1,
Phase 2, or Phase 3
• Phase 1 includes the initial introduction of an
investigational drug into humans and is primarily
for the purpose of assessing safety.
• Phase 1 studies are designed to determine the
human pharmacology of the drug, structureactivity relationship, side effects associated
with increasing doses, and if possible, early
evidence of effectiveness.
• Phase 2 trials are controlled clinical studies to
evaluate the effectiveness of a drug in patients
with the condition for which the drug is
intended and to assess side effects and risks
that may be revealed. Because this phase uses
patients as subjects, side effects or toxicity
symptoms that were not shown in the preclinical
animal studies or in Phase 1 studies with
healthy volunteers may be revealed for the
first time.
• Phase 3 studies may include several hundred to
several thousand patients in controlled and
uncontrolled trials.The objective is to determine
the usefulness of the drug in an expanded
patient base.
• (7) Clinical Study Controls and Designs
• Phase 2 and some Phase 3 studies are controlled,
that is, the effects of the investigational drug
are compared with another agent.The second
agent may be a placebo (placebo control) or an
active drug (positive control), a standard or
comparator drug product.
• For studies that are blinded, the identities of
the investigational drug and the control and
controls are not revealed to certain participants
to decrease bias
• In designing a clinical trial, many addition factors
are considered, including the scheme of the
study design and the duration of the treatment
• (8) Drug dosage and Terminology
•
A major part of any clinical drug is the
determination of a drug’s safe and effective dose.
Dose and dose ranging studies are conducted
during Phase 2 and concluded during Phase 3
clinical trials.
•
The safe and effective dose of a drug depends
on a number of factors, including characteristics
of the drug substances, the dosage form and its
route of administration, and a variety of patient
factors including age, body weight, general health
status, any pathologic conditions, and concomitant
drug therapy. All of these factors and others are
integral to clinical drug trials
•
•
•
•
•
•
The dose of a drug may be described as an
amount that is enough but not too much; the idea is
to achieve the drug’s optimum therapeutic effect
with safety but at the lowest possible dose
The effective dose of a drug may be different
for different patients.
Usual adult dose; usual dosage range;usual
pediatric dose
The schedule of dosage, or the dosage regimen,
is determined during the clinical investigation and is
based largely on a drug’s inherent duration of action,
its pharmacokinetics, and the characteristics of the
dosage form.
Initial dose; priming dose; loading dose;
Prophylactic dose (预防剂量); therapeutic dose
To provide systemic effects, a drug must be
absorbed from its routs of administration at a
suitable rate, be distributed in adequate
concentration to receptor sites, and remain there
for a sufficient period.
Minimum effective concentration (MEC);
Minimum toxic concentration (MTC); Median
effective dose; therapeutic index
Some factors of patients considered in determining
a drug’s dose in clinical investigations and in
medical practice include the following:
Age,Body weight, Body Surface Area, Sex,
Pathologic state,Torlerance, Concomitant Drug
Therapy,Time and Conditions of Administration,
Dosage Form and Route of Administration
• (9)Treatment IND
• A treatment IND or a treatment protocol permits
the use of an investigational drug in the trentment
of patients not enrolled in the clinical study but
who have a serious or immediately life-threatening
disease for which there is non satisfactory
alternative therapy.
• (10) IND for an Orphan Drug
• (11) Withdrawal or Termination of an IND
• The New Drug Application
• If the three phases of clinical testing during the
IND period demonstrate sufficient drug safety
and therapeutic effectiveness, the sponsor may
file a NDA with the FDA. This filing may be
proceded by a pre-NDA meeting between the
sponsor and the FDA to discuss the content and
format of the new drug application.
• The purpose of the NDA is to gain permission to
market the drug product in the United states.
• (1) General Content of the NDA Submission
•
•
•
•
•
•
•
•
•
(2) Drug Product Labeling
(a) Description of product
(b)Clinical pharmacology;
(c) Indications and usage
(d) Contraindications
(e) Warnings (f) Precautions
(g) Adverse reactions
(h) drug abuse and dependence (i) Overdosage
(j) Dosage and administration (k) How supplied
• FDA Review and Action Letters
• The completed NDA is carefully reviewed by the
FDA, which decides whether to allow the sponsor
to market the drug, to disallow marketing, or to
require additional data before rendering a
judgement.
• Phase 4 stuidies and Postmarketing
Surveillance
• The receipt of marketing status for a new drug
product does not necessarily end a sponsor’s
investigation of the drug. Continued clinical
investigations, often called Phase 4 studies.
• Annual Reports
• Supplemental, Abbreviated, and
Other applications
• Supplemental New Drug Application
•
A sponsor of an approved NDA may make
changes in that application through the filing of a
supplemental new drug application (SNDA)
• Abbreviated New Drug Application
•
An abbreviated new drug application (ANDA) is
one in which nonclinical laboratory studies and
clinical investigations may be omitted, except
those pertaining to the drug’s bioavailablility
• Biologics License Application
• Animal Drug Applications
• Medical Devices
• International Conference on
Harmonization of Technical
Requirements for Registration of
Pharmaceuticals for Human Use
Questions
1. Describe the methods of drug discovery
2. Define the following phrases:
- prodrugs
- a lead compound
- a goal drug
3. What physical and chemical properties of
drug substances must be characterized
during preformulation studies? Explain.
4. What biological characterization should
be studied in drug development process？
新药制剂的研究与申报
• 《药品注册管理办法》适用于在中华
人民共和国境内从事药物研究和临床
研究，申请药物临床研究、药品生产
或者进口，以及进行相关的药品注册
检验、监督管理。
一、药品注册申请
• 药品注册是指依照法定程序，对拟上市
销售的药品的安全性、有效性、质量可
控性等进行系统评价，并作出是否同意
进行药物临床研究、生产药品或者进口
药品而决定的审批过程，包括对变更药
品批准证明文件的申请及其附件中声明
内容的审批。
• 药品注册申请包括新药申请、已有国家标准药
品的申请和进口药品申请及其补充申请。
• 新药申请是指未曾在中国境内上市销售药品的
注册申请。已上市药品改变剂型、改变给药途
径的，按照新药管理。
• 已有国家标准药品的申请是指在国内已经生产
由国家药品监督管理局颁布的标准药品注册申
请。
• 进口药品申请是指在境外生产的药品在中国上
市销售的注册申请。
• 补充申请是指新药申请、已有国家标准药品的
申请或者进口药品申请经批准后，改变、增加
或取消原批准事项或内容的注册申请。
• 审批过程中的药品注册申请、已批准的临床研
究申请需进行相应变更的，以及新药技术转让、
进口药品分包装、药品试行标准转正，按补充
申请办理。
• 国家食品药品监督管理局主管全国药品注册管
理工作，负责对药品的临床研究、药品生产和
进口的审批。
• 网址：http://www.sda.gov.cn
二、新药的分类
（一）化学药品注册分类
1.未在国内外上市销售的药品
① 通过合成或者半合成的方法制得的原料药及
其制剂；
② 天然物质中提取或者通过发酵提取的新的有
效单体及其制剂；
③ 用拆分或者合成等方法制得的已知药物中的
光学异构体及其制剂；
④ 由已上市销售的多组分药物制备为较少组分
的药物；
⑤ 新的复方制剂
（一）化学药品注册分类
2.改变给药途径且尚未在国内外上市销售的
制剂。
3.已在国外上市销售，但尚未在国内上市销
售的药品
①已在国外上市销售的原料药及其制剂；
②已在国外上市销售的复方制剂；
③改变给药途径并已在国外上市销售的制剂。
（一）化学药品注册分类
4.改变已上市销售盐类药物的酸根、碱基
（或者金属元素），但不改变其药理作
用的原料药及其制剂。
5.改变国内已上市销售药品的剂型，但不
改变给药途径的制剂。
6.已有国家药品标准的原料药或者制剂。
（二）中药、天然药物注册分类
1.未在国内上市销售的重要、天然药物中提取的
有效成分及其制剂。
2.未在国内上市销售的来源于植物、动物、矿物
等药用物质制成的制剂。
3.中药材的代用品。
4.未在国内上市销售的中药材新的药用部位制成
的制剂。
5.未在国内上市销售的由中药、天然药物中提取
的有效部位制成的制剂。
6.未在国内上市销售的由中药、天然药物制成的
复方制剂。
7.未在国内上市销售的由中药、天然药物
制成的注射剂。
8.改变国内已上市销售药品给药途径的制
剂。
9.改变国内已上市销售药品剂型的制剂。
10.改变国内已上市销售药品工艺的制剂。
11.已有国家标准的中成药和天然药物制
剂。
三、申请新药需上报的项目
（一）综述资料
1、药品名称。
2、证明性文件。
3、立题目的与依据。
4、对主要研究结果的总结及评价。
5、药品说明书样稿、起草说明及最新参考
文献。
6、包装、标签设计样稿。
（二）药学研究资料
7、药学研究资料综述。
8、原料药生产工艺的研究资料及文献资料；制剂处
方及工艺的研究资料及文献资料。
9、确证化学结构或者组份的试验资料及文献资料。
10、质量研究工作的试验资料及文献资料。
11、药品标准草案及起草说明，并提供标准品或者
对照品。
12、样品的检验报告书。
13、辅料的来源及质量标准。
14、药物稳定性研究的试验资料及文献资料。
15、直接接触药品的包装材料和容器的选择依据及
质量标准
（三）药理毒理研究资料
16、药理毒理研究资料综述。
17、主要药效学试验资料及文献资料。
18、一般药理研究的试验资料及文献资料。
19、急性毒性试验资料及文献资料。
20、长期毒性试验资料及文献资料。
21、过敏性（局部、全身和光敏毒性）、溶
血性和局部（血管、 皮肤、粘膜、肌肉等）
刺激性等主要与局部、全身给药相关的特
殊安全性试验研究和文献资料。
22、复方制剂中多种成份药效、毒性、药
代动力学相互影响的试验资料及文献
资料。
23、致突变试验资料及文献资料。
24、生殖毒性试验资料及文献资料。
25、致癌试验资料及文献资料。
26、依赖性试验资料及文献资料。
27、动物药代动力学试验资料及文献资料。
（四）临床研究资料
28、国内外相关的临床研究资料综述。
29、临床研究计划及研究方案。
30、临床研究者手册。
31、知情同意书样稿、伦理委员会批准件。
32、临床研究报告。
四、申报新制剂的主要内容
1.处方、制备工艺、辅料等
2.稳定性试验
3.溶出度或释放度试验
4.生物利用度