Pharmaceutical Equivalence

Medicinal products are pharmaceutically equivalent if they contain the same amount of  the  same  active  substance(s)  in  the  same  dosage  form  that  meet  the  same  or comparable   standards. Pharmaceutical   equivalence   does not   necessarily   imply bioequivalence as differences in the excipients and/or the manufacturing process can lead to faster or slower dissolution and/or absorption.

Drug products are considered pharmaceutical equivalents if they contain the same active  ingredient(s),  are  of  the  same  dosage  form,  route  of  administration  and  are identical  in  strength  or  concentration  (e.g.,  chlordiazepoxide  hydrochloride,  5mg capsules).  Pharmaceutically  equivalent  drug  products  are  formulated  to  contain  the same amount of active ingredient in the same dosage form and to meet the same or compendial  or  other  applicable  standards (i.e., strength, quality,  purity,  and  identity), but  they  may  differ  in  characteristics  such  as  shape,  scoring  configuration,  release mechanisms,   packaging,   excipients   (including   colors,   flavors,   preservatives), expiration time, and, within certain limits, labeling.

《化学药品注册分类及申报资料要求》

化学药品3类为境内生产的仿制境外已上市境内未上市原研药品的药品，具有与参比制剂相同的活性成份、剂型、规格、适应症、给药途径和用法用量，并证明质量和疗效与参比制剂一致。

化学药品4类为境内生产的仿制境内已上市原研药品的药品，具有与参比制剂相同的活性成份、剂型、规格、适应症、给药途径和用法用量，并证明质量和疗效与参比制剂一致。

《仿制药质量和疗效一致性评价工作中改盐基药品评价一般考虑》

药学研究均要求与被改盐基药品对照，进行对比试验，并对改盐基药品与被改盐基药品在各项目的异同与优劣进行评价。改盐基药品质量应与被改盐基药品的参比制剂质量相当。

Pharmaceutical Alternative

Pharmaceutical  alternatives  are  medicinal  products  with  different  salts,  esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active moiety, or which differ in dosage form or strength.

Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety, but are different salts, esters, or complexes of that moiety, or are different dosage forms or strengths(e.g., tetracycline hydrochloride, 250mg capsules vs.  tetracycline  phosphate  complex,  250mg  capsules;  quinidine  sulfate,  200mg tablets  vs.  quinidine  sulfate,  200mg  capsules).  Data  are  generally  not  available  for FDA to make the determination of tablet to capsule bioequivalence. Different dosage forms  and  strengths  within  a  product  line  by  a  single  manufacturer  are  thus pharmaceutical  alternatives,  as  are  extended-release  products  when  compared  with immediate-release or standard-release formulations of the same active ingredient.

《仿制药质量和疗效一致性评价工作中改盐基药品评价一般考虑》

改盐基药品系指制剂中使用的原料药在美国、欧盟或日本均未获准使用或无法确定含有相同原料药的参比制剂的药品。

如果活性成分相同，仅成盐形式不同，称为改盐基药品，包括改变已知盐类活性成分的酸根、碱基或金属离子，对游离形式药品成盐或把成盐药品改为游离形式等原料药与制剂。

原则上讲，通过改变成盐形式制成的药品应不改变其药理作用，仅改变其理化性质（如溶解度、稳定性等），以适应储存、生产或临床用药的需要。

《化学药品注册分类及申报资料要求》

2.1含有用拆分或者合成等方法制得的已知活性成份的光学异构体，或者对已知活性成份成酯，或者对已知活性成份成盐（包括含有氢键或配位键的盐），或者改变已知盐类活性成份的酸根、碱基或金属元素，或者形成其他非共价键衍生物（如络合物、螯合物或包合物），且具有明显临床优势的药品。

化学药品2类为改良型新药，在已知活性成份基础上进行优化，应比改良前具有明显临床优势。已知活性成份指境内或境外已上市药品的活性成份。该类药品同时符合多个情形要求的，须在申报时一并予以说明。

Bioequivalence

Two  medicinal  products  containing  the  same  active  substance  are  considered bioequivalent  if  they  are  pharmaceutically  equivalent  or  pharmaceutical  alternatives and their bioavailabilities(rate and extent) after administration in the same molar dose lie within acceptable predefined limits.

Bioequivalence means the absence of a significant difference inthe rate and extent to  which  the  active  ingredient  or  active  moiety  in  pharmaceutical  equivalents  or pharmaceutical  alternatives  becomes  available  at  the  site  of  drug  action  when administered  at  the  same  molar  dose  under  similar  conditions  in  an  appropriately designed study.

1.         以等效为立题依据的改盐基药品，开展与被改盐基药品参比制剂的生物等效性研究；

2.         以优效为立题依据的改盐基药品，建议以被改盐基药品作为参比制剂，进行药代动力学研究、药代动力学研究/药效动力学研究和（或）相应的临床试验。

Therapeutic Equivalence

Acts

Directive 2001/83/EC

FD&C Act

中华人民共和国药品管理法

Generics application

Possible

Not possible

Possible（3，4类）

Hybrid application

Possible

Possible

Possible （2.1类）

Basis

Article 10(3), Directive 2001/83/EC

505(b)(2), FD&C Act

化学药品注册分类及申报资料要求

Full dossier

Possible

Possible

Possible

When?

New dosage form, strength, route of admin, indication, change to substance

New dosage form, strength, route of admin, indication, change to substance

结构、剂型、处方工艺、给药途径、适应症等进行优化，且具有明显临床优势的药品

Required for different salt?

Only if different properties with respect to safety and/or efficacy

Yes

从药品的理化性质、生物学特性、临床需要等方面分析论证改盐基药品的科学性、合理性和必要性。

What to submit?

No full dossier. Applicant relies in part on innovator’s data, provides some data himself

No full dossier. Applicant relies in part on innovator’s data, provides some data himself

No full dossier. Applicant relies in part on innovator’s data, provides some data himself

Market exclusivity?

No

0-5 years

-

New IP?

Possible

Possible

-

Patent term

20 years

20 years

-

Additional patent protection / data exclusivity

Up to 5 years SPC (Supplementary Protection Certificate)

Up to 5 years Hatch-Waxman Act

-

Regulatory protection period

8 +2 years(data protection + market exclusivity)

5 +x years(data protection + FDAs dossier evaluation time)

-

Sum of maximum total patent protection and/or data protection period after MA

≤ 15 years

≤ 14 years

-