FDA發(fā)布咀嚼片關(guān)鍵質(zhì)量屬性指導(dǎo)原則（中英文對(duì)照）
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This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page. 該指南草案定稿后，代表FDA對(duì)這一主題當(dāng)前的想法，并未賦予任何人權(quán)利，且對(duì)FDA或公眾不具有任何約束力。如果滿足適用的法規(guī)和條例要求，也可以使用另外一種方法。如需討論另外一種方法，請(qǐng)與本指南封面中列出的FDA工作人員聯(lián)系。 |
I. INTRODUCTION
I.引言
Thisguidance provides manufacturers of chewable tablets for human use with theCenter for Drug Evaluation and Research’s (CDER) current thinking on thecritical quality attributes that should be assessed during the development ofthese drug products.2 This guidance also provides recommendationsabout submitting developmental, manufacturing, and labeling information forchewable tablets that must be approved by CDER before they can be distributed.The recommendations in this guidance apply mainly to new drug applications(NDAs), abbreviated new drug applications (ANDAs),3 and certainchemistry, manufacturing, and controls (CMC) supplements to these applications.4 some of therecommendations about the submission of developmental information may alsoapply to investigational new drug applications (INDs). The recommendationsabout assessing critical quality attributes apply to all chewable tablets forhuman use, including non-application products.
本指南向生產(chǎn)者提供了藥品審評(píng)研究中心（CDER）對(duì)人用咀嚼片在研發(fā)過(guò)程中應(yīng)評(píng)估的關(guān)鍵質(zhì)量屬性的當(dāng)前想法2。該指南也提供了必須向CDER提交并被其批準(zhǔn)的咀嚼片的研發(fā)、生產(chǎn)及說(shuō)明書(shū)信息的建議。該指南的這些建議主要針對(duì)新藥申請(qǐng)（NDAs）、仿制藥申請(qǐng)（ANDAs）3和一些化學(xué)、生產(chǎn)和質(zhì)控（CMC）補(bǔ)充申請(qǐng)4。某些建議同樣適合于研究性新藥申請(qǐng)（即新藥臨床申請(qǐng)，INDs）。關(guān)于評(píng)估關(guān)鍵質(zhì)量屬性的建議適用于所有人用咀嚼片，包括非申請(qǐng)產(chǎn)品。
Ingeneral, FDA’s guidance documents do not establish legally enforceableresponsibilities. Instead, guidances describe the Agency’s current thinking ona topic and should be viewed only as recommendations, unless specificregulatory or statutory requirements are cited. The use of the word should inAgency guidances means that something is suggested or recommended, but notrequired.
通常，FDA的指導(dǎo)文件不具有法律強(qiáng)制性，指南中描述的主題僅代表FDA機(jī)構(gòu)目前的看法，只作為建議，除非是引用具體的法規(guī)或條例要求。建議或推薦使用該指導(dǎo)原則，但不是必須的。
II. BACKGROUND
II.背景
Chewabletablets are an immediate release (IR) oral dosage form intended to be chewedand then swallowed by the patient rather than swallowed whole. They should be designed to have a pleasanttaste and be easily chewed and swallowed. Chewable tablets should be safe and easy to use in a diverse patientpopulation, pediatric, adult, or elderly patients, who are unable or unwillingto swallow intact tablets due to the size of the tablet or difficulty withswallowing. The availability of safe, easy-to-use dosage forms is important inclinical practice. Chewable tablets are available for many over-the-counter(OTC) and prescription drug products.
咀嚼片是患者經(jīng)咀嚼后立即釋放的口服劑型，而不是整個(gè)吞咽。其應(yīng)被設(shè)計(jì)為可口的味道且易于咀嚼和吞咽。咀嚼片應(yīng)是安全的，易于那些因片子大小或吞咽困難導(dǎo)致不能或不愿吞服的特殊人群、兒童、成年、或老年患者服用。能獲得安全的、易于服用的劑型在臨床實(shí)踐中非常重要。在許多OTC和處方藥中均有咀嚼片。
TheUnited States Pharmacopeia (USP) recognizes and differentiates between twotypes of chewable tablets: (1) thosethat may be chewed for ease of administration, and (2) those that must bechewed or crushed before swallowing to avoid choking and/or to ensure therelease of the active ingredient.5 The concepts in this guidance are applicable to both types of chewabletablets.
USP藥典中識(shí)別和區(qū)分兩種類(lèi)型的咀嚼片：（1）可以咀嚼以方便服用的咀嚼片；（2）必須咀嚼或壓碎以避免吞咽窒息和/或確保活性成分充分釋放的咀嚼片5。本指南中的概念適用于這兩種類(lèi)型的咀嚼片。
Adverseevents for chewable tablets can include gastrointestinal (GI) obstructionresulting from patients swallowing whole or incompletely chewed tablets, as wellas tooth damage and denture breakage resulting from excessive tablet hardness.6 A related potential adverse event thatsponsors should also consider is esophageal irritation from chewabletablets. A review of numerous approveddrug product applications for chewable tablets revealed that in certain casescritical quality attributes such as hardness, disintegration, and dissolutionwere not given as much consideration as may have been warranted. This was evidenced by instances of incompletemonitoring of all relevant critical quality attributes or the use of widelyranging values that were not justified as acceptance criteria. In addition, a wide variation in analyticalprocedures has been reported.7,8,9
咀嚼片的不良反應(yīng)包括患者整片吞咽或不完全咀嚼導(dǎo)致的胃腸道（GI）阻塞，以及片劑過(guò)硬導(dǎo)致牙齒損傷和假牙破損6。也應(yīng)考慮咀嚼片引起的食道刺激這一潛在不良事件。從過(guò)去批準(zhǔn)的很多咀嚼片來(lái)看，許多產(chǎn)品對(duì)硬度、崩解時(shí)限、溶出度等關(guān)鍵質(zhì)量屬性的考察仍不充分，例如，對(duì)所有相關(guān)的關(guān)鍵質(zhì)量屬性監(jiān)管不完全，或質(zhì)量指標(biāo)范圍很寬泛但未證明其在可接受的標(biāo)準(zhǔn)之內(nèi)。此外，據(jù)報(bào)道，分析方法也存在很大差異7,8,9。
Thisguidance describes the critical quality attributes that should be consideredwhen developing chewable tablets and recommends that the selected acceptancecriteria be appropriate and meaningful indicators of product performancethroughout the shelf life of the product.
本指南建議了開(kāi)發(fā)咀嚼片時(shí)應(yīng)考慮的關(guān)鍵質(zhì)量屬性、可選擇的合適的可接受標(biāo)準(zhǔn)、產(chǎn)品有效期內(nèi)的有意義的產(chǎn)品性能指標(biāo)。
III.DISCUSSION
III.討論
Avariety of physical characteristics should be considered in the manufacturingprocess for chewable tablets. An idealchewable tablet should be:
•Easy to chew
•Palatable (taste masked or of acceptable taste)
•Of appropriate size and shape10
•Able to disintegrate readily to minimize aspiration and facilitate dissolution.
在咀嚼片劑生產(chǎn)工藝中，應(yīng)考慮各種物理特性。理想的咀嚼片應(yīng)為：
•易于咀嚼
•味道可口（掩味或可接受的味道）
•尺寸及形狀適中10
•易崩解，以方便吞咽和活性成分溶出
Criticalquality attributes for chewable tablets should include hardness,disintegration, and dissolution, as well as all factors that may influence drugbioavailability and bioequivalence. Inaddition, careful attention should be given to tablet size, thickness, andfriability, as well as taste, which may impact the ability or willingness of apatient to chew the chewable tablet (i.e., a patient may swallow whole, ratherthan chew, a bad tasting tablet). Nosingle quality characteristic should be considered sufficient to control theperformance of a chewable tablet. Instead, the goal should be to develop theproper combination of these attributes to ensure the performance of thechewable tablet for its intended use.
咀嚼片的關(guān)鍵質(zhì)量屬性包括硬度、崩解時(shí)限、溶出度以及其他影響生物利用度和生物等效性的因素。另外，應(yīng)重視片劑的形狀、厚度、脆碎度和味道，這些會(huì)影響患者服用咀嚼片的能力和意愿（即：患者因味道不好可能整個(gè)吞咽，而不是咀嚼）。充分控制咀嚼片的性能，不能只考慮單一的質(zhì)量屬性，而應(yīng)考慮質(zhì)量屬性的合適組合，從而確保咀嚼片達(dá)到預(yù)期的用途。
A. Hardness
A.硬度
Thehardness of chewable tablets should be such that they withstand the rigors ofmanufacturing, packaging, shipping, and distribution, as well as be easilychewed by the intended patient population. Hardness is generally measured asthe force needed to break the tablet in a specific plane. Tablet hardness maybe measured and expressed in a variety of units. Applications submitted to FDA should use thesame unit of measure in reporting results and specifications. including: kilopond (kp), kilogram-force(kgf), Newton (N), and Strong-Cobb Units(scu). 1 kp = 1 kgf = 9.8 N = 1.4 scu. Publicstandards also exist to ensure consistent measurement of the tablet hardness(Tablet Breaking Force11). Tablet hardness may be used to determinethe chewing difficulty index (see Appendix I).
咀嚼片的硬度要求既能承受生產(chǎn)、包裝、運(yùn)輸、分發(fā)過(guò)程中的外力沖擊，又要求便于目標(biāo)患者人群的咀嚼。硬度通常是測(cè)定在特定平面上使藥片破裂所需力的大小。硬度可以用多種單位表示。向FDA提交申請(qǐng)時(shí)，在報(bào)告結(jié)果和說(shuō)明中，應(yīng)使用相同的度量單位。包括：千克磅(kp), 千克力 (kgf), 牛頓(N)和Strong-Cobb單位(scu)。換算關(guān)系為1 kp = 1 kgf = 9.8 N = 1.4 scu。有公共標(biāo)準(zhǔn)（據(jù)參考文獻(xiàn)是USP藥典標(biāo)準(zhǔn)）來(lái)確保片劑硬度測(cè)量的一致性（片劑脆碎度11），片劑硬度可用于確定咀嚼難度指數(shù)（見(jiàn)附錄Ⅰ）。
B. Disintegration
B．崩解時(shí)限
Thetime required for a tablet to break up into small particles is itsdisintegration time. For chewabletablets, disintegration time should be short enough to prevent GI obstructionin the event a tablet is not completely chewed by the patient. Usually, thepresence of the correct type and amount of a disintegrant facilitates rapiddisintegration of the tablet.12 In vitro disintegration testing should beconducted using intact tablets in suitable medium using established disintegrationequipment (such as USP Disintegration Apparatus) and methods.13
崩解時(shí)限是指藥片從整片破碎成細(xì)小微粒的時(shí)間。對(duì)于咀嚼片，崩解時(shí)間應(yīng)足夠短，以免患者沒(méi)有充分咀嚼發(fā)生胃腸道阻塞。通常，選用正確類(lèi)型及使用量的崩解劑有利于片劑迅速崩解12。體外崩解試驗(yàn)應(yīng)使用完整片劑、在適當(dāng)?shù)慕橘|(zhì)、用已確立的崩解裝置（例如USP崩解儀）和方法進(jìn)行13。
C. Dissolution
C.溶出度
Drugabsorption from chewable tablets depends on the release of the drugsubstance(s) from the intact or the chewed tablets; therefore, in vitrodissolution testing of chewable tablets should follow the principles of dissolutiontesting of conventional IR tablets.14 That is, the active pharmaceuticalingredient(s) of the chewable tablets should adequately dissolve out of thetablet with or without chewing.
咀嚼片的吸收取決于整片或咀嚼后的藥物釋放。因此，咀嚼片的體外溶出試驗(yàn)應(yīng)當(dāng)遵循常規(guī)速釋片的溶出試驗(yàn)原則14，即：咀嚼片中的活性成分在咀嚼或未咀嚼情況下都應(yīng)充分溶出。
Forproduct characterization during development in vitro dissolution testing shouldbe conducted on intact tablets in at least four media, such as water, aqueousmedia at pH 1.2, buffer pH 4.5, and buffer pH 6.8, with established dissolutionmethods using equipment such as USP Apparatus 1 (basket), USP Apparatus 2(paddle), or USP Apparatus 3 (reciprocating cylinder).15
開(kāi)發(fā)過(guò)程中的體外溶出試驗(yàn)應(yīng)當(dāng)使用完整片劑在至少4種介質(zhì)中進(jìn)行，例如水、pH1.2、pH4.5、pH6.8緩沖液；采用USP藥典公認(rèn)的溶出方法試驗(yàn)，例如方法1（轉(zhuǎn)籃法）、方法2（槳法）或方法3（往復(fù)筒法）15。
D. Performance in Simulated Physiological Media
D.生理介質(zhì)模擬實(shí)驗(yàn)
Chewabletablets should also be evaluated using dissolution media such as simulatedfasted and fed state gastric and intestinal fluids with enzymes (biorelevantdissolution media). Hardness should also be tested after brief (30-120s)exposures to small quantities (1-2mL) of human or simulated saliva. Suchstudies may provide a better understanding of in vivo performance of thechewable tablets16. In vitro testing in physiological media,consistent with the targeted patient population characteristics may supportfurther characterization of the drug product and its critical qualityattributes.
咀嚼片劑應(yīng)當(dāng)使用模擬空腹和餐后胃腸生理環(huán)境的溶出介質(zhì)（生物相關(guān)介質(zhì)）進(jìn)行評(píng)價(jià)。硬度測(cè)試，應(yīng)短時(shí)（30-120S）暴露于少量（1-2ml）人類(lèi)或模擬唾液后進(jìn)行。這些研究可以更好的了解咀嚼片的體內(nèi)性能。16在體外生理介質(zhì)模擬實(shí)驗(yàn)中，采用與目標(biāo)患者人群一致的生理介質(zhì)可能會(huì)對(duì)該藥品進(jìn)一步的鑒定和關(guān)鍵質(zhì)量屬性提供數(shù)據(jù)支持。
E. Biowaiver and Postapproval Considerations
E.生物等效性豁免及上市后的注意事項(xiàng)
Thesolubility and permeability characteristics of the drug substance may be usedto determine where the drug fits within the Biopharmaceutics ClassificationSystem (BCS). Depending on the BCS classification of the drug substance,proposals for waiver of bioequivalence (BE) studies may be considered forchewable tablets17. Changes in the chemistry, manufacturing andcontrols after approval of the chewable tablets should be made in conformancewith the principles outlined in the Scale-up and Post-Approval ChangesImmediate Release (SUPAC IR) guidance document18.
藥物的溶解度和滲透性可以用來(lái)確定藥物的生物藥劑學(xué)分類(lèi)系統(tǒng)（BCS）。根據(jù)藥物的BCS分類(lèi)，咀嚼片可提出生物等效性（BE）研究豁免的申請(qǐng)17。咀嚼片上市后發(fā)生化學(xué)、生產(chǎn)及質(zhì)控工藝變更時(shí)，應(yīng)遵從《速釋口服固體制劑：放大生產(chǎn)和批準(zhǔn)后變更》（SUPAC IR）指南18。
IV. RECOMMENDATIONS
IV. 建議
Thefollowing general and specific recommendations should be considered during thedevelopment phase of a chewable tablet.
下面的一般和具體建議，應(yīng)在咀嚼片的開(kāi)發(fā)階段考慮。
Potentialproduct design and development considerations should include: disintegrant(s)to facilitate release of the active ingredient, and sweeteners and flavoringagents for taste-masking19. The possibility of the interaction ofexcipients with each other and/or the drug substance(s), and their likelyimpact on the manufacturing process, should be explored.
產(chǎn)品設(shè)計(jì)和開(kāi)發(fā)階段應(yīng)考慮的方面包括：促進(jìn)活性成分釋放的崩解劑，增甜劑和用于掩味的調(diào)味劑19。應(yīng)研究可能出現(xiàn)的輔料之間的相互作用和/或輔料與藥物之間的相互作用，及這些相互作用可能對(duì)生產(chǎn)工藝的影響。
Thefollowing information should be collected either during the conduct of pivotalclinical studies and reported in the subsequent NDA:
1.Were the chewable tablets swallowed intact (i.e., without breaking) or afterbeing thoroughly chewed?
2.If swallowed intact, does the shape and size of chewable tablet pose a chokingor bowel obstruction risk? 20
3.If water was used to aid swallowing, what was the volume?
4.What was the subject’s sensory experience (e.g., taste, mouth feel, andaftertaste)? 21,22
下面的信息應(yīng)該在臨床研究期間收集并在隨后的NDA申請(qǐng)資料中報(bào)告：
1.該咀嚼片可以完整吞服（不破壞）還是應(yīng)該徹底咀嚼后吞服？
2.如果完整吞服，該咀嚼片的形狀和大小是否有造成窒息或腸梗阻的風(fēng)險(xiǎn)？20
3.如果患者可以用水幫助吞咽，水的用量是多少？
4.患者用藥的感官體驗(yàn)如何（例如，味覺(jué)、口感、余味）？21,22
ForANDA applications, general information such as subject’s sensory experience(acceptability of taste, mouthfeel, and aftertaste) and ease of swallowing – incase of tablets swallowed intact –can be collected during the conduct ofbioequivalence studies and reported in the subsequent ANDA submissions.
對(duì)于ANDA申請(qǐng)，一般要求，在生物等效性研究期間收集患者的用藥體驗(yàn)（味道可接受性、口感和余味）和在片劑整個(gè)吞服時(shí)的吞咽改善，在后續(xù)ANDA申報(bào)資料中報(bào)告。
Thepotential for buccal absorption of the drug substance should be evaluated anddescribed in the NDA. The importance of any buccal absorption may depend on thesolubility and permeability characteristics of the drug substance, itsstability in saliva (over a pH range 6.0 to 7.5), and whether it undergoesextensive first-pass metabolism.
對(duì)于藥物潛在的口腔吸收應(yīng)評(píng)估并在NDA申請(qǐng)中說(shuō)明。藥物口腔吸收的重要性主要取決于藥物的溶解性和滲透性，藥物在唾液中的穩(wěn)定性（pH6.0~7.5），以及藥物是否有首過(guò)代謝。
Stabilityin the buccal environment can usually be assessed in vitro. For example,studies at the applicable pH range over a short period of time (e.g., <5min) showing minimal drug substance release or lack of degradation of the drugsubstance may be adequate to demonstrate short-term stability in the buccalenvironment.
通常，可以采用體外研究評(píng)估藥物在口腔環(huán)境中的穩(wěn)定性。例如，在合適的pH值范圍內(nèi)，研究短時(shí)間內(nèi)（例如，<5分鐘）藥物的最小釋放或降解可得出口腔環(huán)境的短期穩(wěn)定性。
A. Critical Quality Attributes
A．關(guān)鍵質(zhì)量屬性
Thehardness, dissolution, and disintegration of the chewable tablet should beestablished early in development. FDA recommends that multiple attributes bestudied to address the performance of the chewable tablet and incorporated inthe product specification. Reliance on only one attribute should beavoided.
咀嚼片研發(fā)早期應(yīng)該研究硬度、溶解度、崩解時(shí)限。FDA建議研究多個(gè)屬性，來(lái)了解咀嚼片的質(zhì)量，并在質(zhì)量標(biāo)準(zhǔn)中制訂。應(yīng)避免只依賴(lài)一個(gè)屬性。
Fordrug products that require filing of an application with the Agency, thedevelopment information should be provided in section 3.2.P.2 (PharmaceuticalDevelopment) of a common technical document (CTD) formatted submission. Theinformation on tablet hardness and chewing difficulty index (see Appendix I)should be provided in section 3.2.P.3.4 (Control of Critical Steps andIntermediates) or section 3.2.P.5.1 (Specification) of a CTD formattedapplication23.
對(duì)于需要在FDA申請(qǐng)的藥品，應(yīng)在CTD文件3.2.P.2（藥品開(kāi)發(fā)）中提供研發(fā)信息。在CTD文件3.2.P.3.4（關(guān)鍵步驟和中間體的控制）或3.2.P.5.1（質(zhì)量標(biāo)準(zhǔn)）中提供片劑硬度和咀嚼難度指數(shù)的信息（見(jiàn)附錄Ⅰ）23。
TheAgency encourages manufacturers of currently approved chewable tablets and nonapplication chewable tablets to reevaluatethe critical quality attributes and ensure appropriate specifications are inplace. Should the Agency have reason to determine that a marketed chewabletablet poses a particular risk to public health because it is difficult to chew(e.g., causes damage to the teeth or dental prosthetics, or GI obstruction),appropriate action will be taken to alleviate the risk to public health.
FDA鼓勵(lì)目前已批準(zhǔn)的咀嚼片和非申請(qǐng)的咀嚼片的生產(chǎn)商重新評(píng)價(jià)其關(guān)鍵質(zhì)量屬性，并確保適當(dāng)?shù)馁|(zhì)量標(biāo)準(zhǔn)。FDA須確定市售咀嚼片是否因咀嚼困難帶來(lái)公共健康風(fēng)險(xiǎn)（例如，對(duì)牙齒或假牙的損傷，或胃腸阻塞），并采取適當(dāng)?shù)拇胧﹣?lái)降低公共健康風(fēng)險(xiǎn)。
Hardness
硬度
oBased on the review of applications and literature sources, the Agencyrecommends that hardness for chewable tablets be kept low (e.g., < 12 kp).
基于申請(qǐng)資料和文獻(xiàn)資料綜述，FDA建議，咀嚼片硬度應(yīng)保持較低（例如，<12KP）。
oA higher hardness value (e.g., >12 kp) may be considered if brief(approximately 30 seconds) exposure to saliva before chewing results insignificant disintegration and/or reduction in hardness of these tablets. Thestudy may be performed in vivo using human volunteers or in vitro for 30seconds exposure, using 1 mL of simulated salivary fluid (see Appendix II).
如果咀嚼片在短時(shí)（約30秒）暴露于唾液中崩解和/或硬度顯著降低，可以考慮較高的硬度值（例如，>12KP）。這項(xiàng)研究可以利用人類(lèi)志愿者體內(nèi)進(jìn)行或在體外30秒暴露于1ml模擬唾液來(lái)進(jìn)行（見(jiàn)附錄II）。
oIn all other cases, the sponsor should provide justification for the proposedhardness, including studies demonstrating that the tablet can be safely chewedby the intended population without damage to teeth, dentures, or other adverseeffects related to chewing these tablets.
在其他情況下，申請(qǐng)者應(yīng)對(duì)所提出的硬度提供理由，包括研究，來(lái)表明該片劑可以被預(yù)期人群安全地咀嚼，而對(duì)牙齒、假牙無(wú)損害，或無(wú)其他與咀嚼相關(guān)的不良影響。
oIn addition to evaluating the hardness of chewable tablets, the sponsor shouldconsider evaluating the tablets for the chewing difficulty index (see AppendixI) both before and after exposure to human saliva.
除了評(píng)估咀嚼片的硬度外，申請(qǐng)者應(yīng)考慮評(píng)估咀嚼片暴露于人的唾液前后的咀嚼難度指數(shù)（見(jiàn)附錄Ⅰ）。
Disintegration and Dissolution
oChewable tablets should typically meet the same disintegration and dissolutionspecifications as IR tablets.
咀嚼片的崩解時(shí)限和溶解度通常應(yīng)符合相同的速釋片的標(biāo)準(zhǔn)要求。
oIn vitro dissolution testing should be conducted on intact chewable tabletssince it is possible that some patients might swallow the tablets withoutchewing. Crushing of the chewable tablets prior to conducting in vitrodissolution testing generally is not recommended since there is no reportedvalidated method for this process to date. Furthermore, this approach would beunlikely to result in experimental conditions simulating a range of chewingpatterns that might be observed in different patient populations. However,additional dissolution assessments may be needed on a case-by-case basis24based on product-specific information.
體外溶出度試驗(yàn)應(yīng)該采用完整的咀嚼片進(jìn)行，因?yàn)橐恍┗颊呖赡軙?huì)不經(jīng)咀嚼而整個(gè)吞服。原來(lái)的體外溶出試驗(yàn)通常將咀嚼片破碎后進(jìn)行，不推薦該方式，因?yàn)槠扑檫^(guò)程未經(jīng)過(guò)驗(yàn)證。此外，這種方法無(wú)法模擬多種試驗(yàn)條件，不能考察不同的患者群體中的咀嚼模式。然而，可能需要基于特定產(chǎn)品的信息，根據(jù)具體情況逐一進(jìn)行溶出評(píng)估24。
oIt is possible to use other methods, as long as the proposed methods aredemonstrated to be equivalent or superior to the existing approaches.
可以使用其他方法，只要可以證明該方法等同或優(yōu)于現(xiàn)有的方法。
• Other Critical Quality Attributes
其他關(guān)鍵質(zhì)量屬性
oOther critical quality attributes applicable to a particular chewable tabletshould be evaluated using Agency recommended methods or using methods that aredemonstrated to be equivalent or superior to the existing approaches.
咀嚼片的其他關(guān)鍵質(zhì)量屬性應(yīng)使用FDA建議的方法，或使用被證明是等同或優(yōu)于現(xiàn)有方法的方法進(jìn)行評(píng)價(jià)。
B. Nomenclatureand Labeling
B. 命名和標(biāo)識(shí)
Aspreviously stated, the USP recognizes and differentiates between two types ofchewable tablets: (1) those that may bechewed for ease of administration, and (2) those that must be chewed and/or crushed before swallowing toavoid choking and to ensure the release of the active ingredient.25These two types of chewable tablets are differentiated by the way they arenamed and labeled.
如前所述，USP藥典中識(shí)別和區(qū)分兩種類(lèi)型的咀嚼片：（1）可以咀嚼以方便服用的咀嚼片；（2）必須咀嚼和/或壓碎以避免吞咽窒息和確?；钚猿煞殖浞轴尫诺木捉榔?/span>25。這兩種類(lèi)型的咀嚼片由它們的命名和標(biāo)簽來(lái)區(qū)分。
•The format “[DRUG] Tablets” will be used for tablets that MAY be chewed orswallowed in their entirety. The labels and labeling for these products willalso include a labeling statement indicating that the tablets MAY be chewed.
格式為“【藥品】片”將用于可以咀嚼或整個(gè)吞服的片劑。對(duì)這些產(chǎn)品的標(biāo)簽和標(biāo)簽說(shuō)明書(shū)將包括該片劑可以咀嚼的標(biāo)記語(yǔ)句。
•The format “[DRUG] Chewable Tablets” will be used for tablets that MUST bechewed and for which there is no alternative route of administration. Thelabels and labeling for these products will also include a labeling statementindicating that the tablets MUST be chewed.
•格式為“【藥品】咀嚼片”將用于必須咀嚼且除了咀嚼無(wú)其他任何可替代服用方法的片劑。對(duì)這些產(chǎn)品的標(biāo)簽和標(biāo)簽說(shuō)明書(shū)將包括該片劑必須咀嚼的標(biāo)記語(yǔ)句。
Tohelp prevent patients from swallowing intact “[DRUG] Chewable Tablets,” it isstrongly recommended that the principle display panel of the container labeland the carton labeling (if applicable) prominently state the following:
為防止患者整個(gè)吞咽“【藥品】咀嚼片”，強(qiáng)烈建議容器標(biāo)簽的主要展示面上和紙箱標(biāo)簽（若適用）上明確聲明如下：
Chewor crush tablets completely before swallowing.
吞咽前徹底咀嚼或徹底粉碎藥片。
Ifspace permits, it is recommended that the following statement be displayed withlesser prominence to reinforce the importance of chewing the tablets:
如果空間允許，則建議下面的語(yǔ)句稍突出顯示，以加強(qiáng)咀嚼片劑的重要性：
Donot swallow tablets whole.
不要整個(gè)吞服藥片。
Additionally,language similar to the previously mentioned statements should appear in the professionallabeling (Highlights of Prescribing Information; Section 2 Dosage andAdministration, and Section 17 Patient Counseling Information), as well as inany accompanying patient information or Medication Guide, if applicable.
此外，類(lèi)似于前面聲明的語(yǔ)言應(yīng)該出現(xiàn)在專(zhuān)業(yè)說(shuō)明書(shū)（處方信息的要點(diǎn)；第2部分劑量和用法，第17部分患者咨詢(xún)資料），任何附帶的患者信息或用藥指南（若適用）。
