选自CFR 211
§211.180 General requirements.(e) Written records required by this part shall be maintained so that data therein can be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures. Written procedures shall be established and followed for such evaluations and shall include provisions for: (1) A review of a representative number of batches, whether approved or rejected, and, where applicable, records associated with the batch. (2) A review of complaints, recalls, returned or salvaged drug products, and investigations conducted under §211.192 for each drug product. (f) Procedures shall be established to assure that the responsible officials of the firm, if they are not personally involved in or immediately aware of such actions, are notified in writing of any investigations conducted under §§211.198, 211.204, or 211.208 of these regulations, any recalls, reports of inspectional observations issued by the Food and Drug Administration, or any regulatory actions relating to good manufacturing practices brought by the Food and Drug Administration. [43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4091, Jan. 20, 1995]
下文选自 USA federal register(rule and regulation)
E. General RequirementsSection 211.180(e) requires thatwritten records be maintained so thatthe data contained therein are availableat least annually for evaluation of thequality standards for drug products.Proposed § 211.180(e)(1) was intendedto correct the misinterpretation that theregulation required the review of everybatch record for every drug productproduced during the year. The proposedrule revised the language to require atleast annually a review of arepresentative number of batch records.
10. One comment noted that currenttechnology makes it possible to usecomputer data to evaluate productquality data to detect adverse trends.The comment asserted that such anapproach permitted more effective andfrequent evaluation of such data.
The agency agrees that technologicaladvances can produce gains in both theaccuracy of data evaluation and thespeed at which the process can beconducted, and FDA encourages the useof technology that helps safeguard theintegrity of the manufacturing process.However, such computerizedinformation must be used as acomplement to, and not as a substitutefor, human judgment and intervention.Computerized assessments must bemonitored by qualified individuals todetect trends that may provide an earlyindication of changes in drug productspecifications or manufacturing orcontrol procedures that merit attentionand intervention. Moreover, otherfactors such as product complaints andrecall information may not be includedin the computer data.
11. Several comments requestedclarification about the types of recordssubject to the batch review requirement.The proposed rule was not intendedto change the types of records subject toannual review, but instead to allowreview of a representative number ofbatches in lieu of examining all recordsfrom every batch. FDA has, therefore,clarified the final rule to require areview of a representative number ofbatches, whether approved or rejected,and where applicable, recordsassociated with those batches.The overall intent of § 211.180(e) is toprovide manufacturers with reliableprocedures for reviewing the qualitystandards for each drug product. Thus,FDA advises that, although this finalrule does not in all cases require anannual review of every batch record,adopting a procedure to check everybatch record would clearly beappropriate if, for example, arepresentative review of batch recordsshowed an adverse trend in quality.
12. One comment advised that somefirms may confuse the requirementswith regard to the annual review ofrepresentative batches with therequirements for batch review prior tothe release of a product under § 211.192.FDA disagrees with the comment. Thefinal rule amends § 211.180(e), whichrequires that written records bemaintained so that data can be used forevaluating, at least annually, the qualitystandards of each drug product. Section211.192, by contrast, specificallyrequires a quality control unit to reviewdrug product production and controlrecords to determine compliance withwritten procedures prior to the releaseof a drug product batch. In brief,§ 211.180(e) involves a retrospectiveoverall evaluation of the adequacy of thequality standards for drug products,while § 211.192 involves acontemporaneous evaluation of a drugbatch to determine its conformity, at thetime of marketing, with current qualitystandards.
13. One comment suggested allowinga biennial review to permit trendanalysis when three or fewer productbatches are produced each year.FDA disagrees with this comment.The agency believes that a 2-yearinterval between formal review ofbatches is inadequate. Potentialproblems with product qualitystandards could go undetected andthereby delay recognition of a need torevise specifications or manufacturingor control procedures. If a serious erroris not detected for a long period, theresulting product could pose a threat topublic health and safety. Moreover, atrend analysis may be performed insituations where only a few batches areproduced annually by using batchesproduced in preceding years.
14. One comment strongly opposedthe proposed changes, stating that everybatch record must be reviewed to detect‘‘drift’’ or changes in specifications forcomponents, manufacturing processes,or other procedures. The commentasserted that, without reviewing everybatch, deleterious changes might beinstituted by a firm employee oremployees without the full knowledgeof their superiors, particularly the firm’sresearch and development group
The agency does not believe suchadditional measures are necessary. ThisCGMP provision does not stand alonebut must be read in context with otherCGMP regulations. Those regulationsprovide a variety of safeguards fordifferent stages and aspects of the drugmanufacturing process. It is the CGMPregulations, taken as a whole, that helpensure drug quality. Moreover, theconsequences of widespread disclosureof problems with drug product qualityresulting from a recall or otherameliorative action are sufficientlysevere to provide most firms with acontinuing incentive to maintainproduct quality. The agency hascarefully reviewed this issue andbelieves that the final rule will notreduce drug product quality(GMP法规的整体控制观念,切忌局部过度冗余评估)
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