III_CRD ._SENT Regulatory_AJ0 Approach_NN1 to_PRP CMC_NP0 Changes_NN2 
As_CJS described_VVN in_PRP 21_CRD CFR_NP0 314.70_CRD ,_PUN 21_CRD CFR_NP0 314.97_CRD ,_PUN and_CJC 21_CRD CFR_NP0 601.12_CRD ,_PUN an_AT0 applicant_NN1 must_VM0 notify_VVI FDA_NN1 about_PRP changes_NN2 in_PRP each_DT0 condition_NN1 (_PUL e.g._AV0 ,_PUN the_AT0 product_NN1 ,_PUN production_NN1 process_NN1 ,_PUN quality_NN1 controls_NN2 ,_PUN equipment_NN1 ,_PUN facilities_NN2 ,_PUN or_CJC labeling_NN1 )_PUR established_VVN in_PRP an_AT0 approved_AJ0 application_NN1 beyond_PRP the_AT0 variations_NN2 already_AV0 provided_VVN for_PRP in_PRP the_AT0 application_NN1 ._SENT The_AT0 reporting_NN1 category_NN1 for_PRP such_DT0 changes_NN2 depends_VVZ on_PRP the_AT0 potential_NN1 to_TO0 have_VHI an_AT0 adverse_AJ0 effect_NN1 on_PRP the_AT0 identity_NN1 ,_PUN strength_NN1 ,_PUN quality_NN1 ,_PUN purity_NN1 ,_PUN or_CJC potency_NN1 of_PRF the_AT0 product_NN1 as_PRP these_DT0 factors_NN2 may_VM0 relate_VVI to_PRP the_AT0 safety_NN1 or_CJC effectiveness_NN1 of_PRF the_AT0 product_NN1 ._SENT Therefore_AV0 ,_PUN changes_NN2 can_VM0 range_VVI from_PRP those_DT0 that_CJT require_VVB approval_NN1 before_PRP implementation_NN1 (_PUL prior_AJ0 approval_NN1 supplement_NN1 (_PUL PAS_NP0 )_PUR )_PUR ,_PUN those_DT0 that_CJT require_VVB notification_NN1 30_CRD days_NN2 before_AV0 (_PUL changes_NN2 being_VBG effected_VVN in_PRP 30_CRD days_NN2 (_PUL CBE-30_CRD )_PUR )_PUR ,_PUN or_CJC upon_PRP implementation_NN1 (_PUL changes_NN2 being_VBG effected_VVN )_PUR ,_PUN and_CJC those_DT0 where_AVQ notification_NN1 can_VM0 be_VBI provided_VVN after_PRP implementation_NN1 (_PUL annual_AJ0 report_NN1 )_PUR ._SENT Some_DT0 of_PRF these_DT0 identified_AJ0 changes_NN2 ,_PUN depending_VVG on_PRP the_AT0 circumstances_NN2 ,_PUN may_VM0 be_VBI more_AV0 appropriately_AV0 submitted_VVN as_PRP an_AT0 original_AJ0 application_NN1 instead_AV0 of_PRF as_AV0 supplements.4_AJ0 
FDA_NP0 has_VHZ conveyed_VVN additional_AJ0 clarification_NN1 regarding_PRP reporting_NN1 of_PRF CMC_NP0 changes_NN2 to_PRP an_AT0 NDA_NP0 ,_PUN BLA_NP0 ,_PUN and_CJC ANDA_NN1 in_PRP guidance_NN1 documents_NN2 specific_AJ0 to_PRP various_AJ0 application_NN1 types_NN2 and_CJC product_NN1 dosage_NN1 forms_NN2 (_PUL see_VVB section_NN1 VII_CRD ._SENT ,_PUN References_NN2 )_PUR ._SENT The_AT0 content_NN1 in_PRP section_NN1 IV_CRD ._SENT ,_PUN Common_AJ0 Changes_NN2 Related_VVN to_PRP Glass_NN1 Vials_NN2 and_CJC Stoppers_NN2 ,_PUN related_VVN to_PRP changes_NN2 to_PRP glass_NN1 vials_NN2 and_CJC stoppers_NN2 for_PRP finished_AJ0 drug_NN1 and_CJC biological_AJ0 products_NN2 includes_VVZ content_NN1 derived_VVN from_PRP the_AT0 referenced_AJ0 guidance_NN1 documents_NN2 ._SENT 
FDA_NP0 applies_VVZ a_AT0 risk-based_AJ0 approach_NN1 to_PRP the_AT0 evaluation_NN1 of_PRF proposed_AJ0 CMC_NP0 changes_NN2 to_PRP a_AT0 CCS_NP0 (_PUL e.g._AV0 ,_PUN changes_NN2 in_PRP components_NN2 ,_PUN composition_NN1 ,_PUN container_NN1 type_NN1 ,_PUN suppliers_NN2 and_CJC manufacturers_NN2 )_PUR ,_PUN taking_VVG into_PRP consideration_NN1 the_AT0 characteristics_NN2 of_PRF the_AT0 specific_AJ0 product_NN1 ._SENT The_AT0 suitability_NN1 and_CJC compatibility_NN1 of_PRF a_AT0 CCS_NP0 depends_VVZ not_XX0 only_AV0 on_PRP the_AT0 properties_NN2 of_PRF a_AT0 container_NN1 ,_PUN but_CJC also_AV0 on_PRP the_AT0 properties_NN2 of_PRF other_AJ0 CCS_NP0 components_NN2 and_CJC their_DPS interactions_NN2 with_PRP the_AT0 drug_NN1 product_NN1 formulation_NN1 over_PRP its_DPS intended_AJ0 shelf_NN1 life_NN1 ._SENT Applicants_NN2 must_VM0 validate_VVI the_AT0 effects_NN2 of_PRF the_AT0 change_NN1 prior_AJ0 to_PRP distribution_NN1 of_PRF the_AT0 drug_NN1 ,_PUN 5_CRD and_CJC ,_PUN as_CJS appropriate_AJ0 ,_PUN conduct_VVB additional_AJ0 qualification_NN1 tests_NN2 or_CJC submit_VVB information_NN1 to_TO0 address_VVI product-_AJ0 specific_AJ0 risks_NN2 as_PRP part_NN1 of_PRF that_DT0 assessment_NN1 ._SENT For_PRP example_NN1 ,_PUN this_DT0 additional_AJ0 information_NN1 to_TO0 be_VBI submitted_VVN to_PRP FDA_NP0 could_VM0 include_VVI studies_NN2 to_TO0 assess_VVI :_PUN the_AT0 effect_NN1 of_PRF formulation_NN1 attributes_NN2 such_DT0 as_PRP high_AJ0 pH_NN1 ;_PUN the_AT0 effect_NN1 of_PRF factors_NN2 that_CJT increase_VVB the_AT0 potential_NN1 for_PRP glass_NN1 delamination_NN1 ,_PUN particulate_NN1 matter_NN1 ,_PUN leachables_NN2 ,_PUN or_CJC interactions_NN2 of_PRF labile_AJ0 molecules_NN2 with_PRP leachables_NN2 (_PUL such_DT0 as_PRP susceptibility_NN1 of_PRF some_DT0 proteins_NN2 to_TO0 interact_VVI with_PRP metal_NN1 ions_NN2 )_PUR ;_PUN or_CJC the_AT0 effect_NN1 of_PRF the_AT0 lyophilization_NN1 process_NN1 on_PRP product_NN1 quality_NN1 ._SENT Finally_AV0 ,_PUN applicable_AJ0 tests_NN2 and_CJC studies_NN2 as_CJS outlined_VVN in_PRP United_NP0 States_NP0 Pharmacopeia_NP0 (_PUL USP_NP0 )_PUR chapters6_NN1 should_VM0 be_VBI conducted_VVN to_TO0 demonstrate_VVI the_AT0 suitability_NN1 of_PRF the_AT0 glass_NN1 vial_NN1 following_VVG a_AT0 change_NN1 ;_PUN such_DT0 tests_NN2 must_VM0 be_VBI conducted_VVN where_CJS needed_VVN to_TO0 ensure_VVI continued_AJ0 compliance_NN1 with_PRP compendial_AJ0 standards_NN2 for_PRP strength_NN1 ,_PUN quality_NN1 ,_PUN or_CJC purity_NN1 of_PRF the_AT0 drug.7_AJ0 FDA_NN1 encourages_VVZ applicants_NN2 to_TO0 submit_VVI the_AT0 appropriate_AJ0 postapproval_NN1 supplement_NN1 type_NN1 as_CJS recommended_VVN by_PRP the_AT0 existing_AJ0 guidance_NN1 documents_NN2 for_PRP proposed_AJ0 changes_NN2 to_PRP the_AT0 CCS_NP0 ._SENT 
As_CJS discussed_VVN in_PRP section_NN1 V._NN0 ,_PUN Tools_NN2 to_PRP Facilitate_VVB Changes_NN2 to_PRP CCS_NP0 Components_NN2 ,_PUN of_PRF this_DT0 guidance_NN1 and_CJC the_AT0 guidance_NN1 for_PRP industry_NN1 Manufacturing_NN1 ,_PUN Supply_NN1 Chain_NN1 ,_PUN and_CJC Drug_NN1 and_CJC Biological_AJ0 Product_NN1 Inspections_NN2 During_PRP COVID-19_AJ0 Public_AJ0 Health_NN1 Emergency_NN1 ;_PUN Questions_NN2 and_CJC Answers_NN2 (_PUL August_NP0 2020_CRD )_PUR ,_PUN 8_CRD FDA_NN1 may_VM0 consider_VVI available_AJ0 risk_NN1 evaluations_NN2 and_CJC product_NN1 quality_NN1 risk_NN1 mitigation_NN1 strategies_NN2 to_TO0 support_VVI a_AT0 lower_AJC reporting_NN1 category_NN1 for_PRP specific_AJ0 changes_NN2 ._SENT FDA_NP0 recommends_VVZ applicants_NN2 use_VVB the_AT0 risk_NN1 management_NN1 principles_NN2 described_VVN in_PRP the_AT0 ICH_NN1 guidance_NN1 for_PRP industry_NN1 Q9_NN1 Quality_NN1 Risk_NN1 Management_NN1 (_PUL June_NP0 2006_CRD )_PUR where_AVQ appropriate_AJ0 ._SENT Whether_CJS or_CJC not_XX0 a_AT0 change_NN1 is_VBZ required_VVN to_TO0 be_VBI reported_VVN to_PRP FDA_NP0 ,_PUN in_PRP accordance_NN1 with_PRP applicable_AJ0 regulations_NN2 ,_PUN 9_CRD FDA_NP0 expects_VVZ all_DT0 changes_NN2 to_TO0 be_VBI appropriately_AV0 managed_VVN by_PRP an_AT0 establishment_NN1 's_VBZ /_PUN facility_NN1 's_POS pharmaceutical_AJ0 quality_NN1 system_NN1 under_PRP the_AT0 applicable_AJ0 current_AJ0 good_AJ0 manufacturing_NN1 practice_NN1 regulations_NN2 in_PRP 21_CRD CFR_NP0 parts_NN2 210_CRD ,_PUN 211_CRD ,_PUN and_CJC 600._CRD Applicants_NN2 should_VM0 also_AV0 refer_VVI to_PRP the_AT0 recommendations_NN2 in_PRP the_AT0 ICH_NN1 guidance_NN1 for_PRP industry_NN1 Q10_NP0 Pharmaceutical_AJ0 Quality_NN1 System_NN1 (_PUL April_NP0 2009_CRD )_PUR ._SENT 
The_AT0 supplement_NN1 for_PRP a_AT0 CCS-related_AJ0 change_NN1 should_VM0 include_VVI information_NN1 to_TO0 support_VVI the_AT0 proposed_AJ0 change_NN1 and_CJC can_VM0 incorporate_VVI certain_AJ0 information_NN1 by_PRP reference_NN1 to_PRP a_AT0 drug_NN1 master_NN1 file_NN1 (_PUL DMF_NP0 )_PUR ,_PUN where_CJS appropriate_AJ0 ._SENT However_AV0 ,_PUN when_CJS incorporating_VVG information_NN1 by_PRP reference_NN1 to_PRP a_AT0 DMF_NP0 ,_PUN the_AT0 supplement_NN1 should_VM0 also_AV0 include_VVI sufficient_AJ0 product-specific_AJ0 information_NN1 to_TO0 support_VVI the_AT0 change_NN1 ._SENT 
Applicants_NN2 are_VBB ultimately_AV0 responsible_AJ0 for_PRP assessing_VVG the_AT0 effects_NN2 of_PRF the_AT0 proposed_AJ0 change_NN1 (_PUL s_ZZ0 )_PUR on_PRP product_NN1 quality_NN1 ,_PUN and_CJC ensuring_VVG that_DT0 information_NN1 to_TO0 support_VVI the_AT0 change_NN1 is_VBZ provided_VVN for_PRP a_AT0 complete_AJ0 submission_NN1 of_PRF a_AT0 supplement_NN1 or_CJC annual_AJ0 report.10_NP0 DMF_NP0 holders_NN2 must_VM0 notify_VVI affected_AJ0 authorized_AJ0 parties_NN2 of_PRF any_DT0 DMF_NP0 changes_NN2 ,_PUN additions_NN2 ,_PUN or_CJC deletions.11_NP0 DMF_NP0 holders_NN2 also_AV0 should_VM0 provide_VVI application_NN1 holders_NN2 with_PRP sufficient_AJ0 information_NN1 to_TO0 determine_VVI the_AT0 appropriate_AJ0 reporting_NN1 procedure_NN1 for_PRP their_DPS applications_NN2 based_VVN on_PRP the_AT0 potential_NN1 to_TO0 have_VHI an_AT0 adverse_AJ0 effect_NN1 on_PRP the_AT0 identity_NN1 ,_PUN strength_NN1 ,_PUN quality_NN1 ,_PUN purity_NN1 ,_PUN or_CJC potency_NN1 of_PRF the_AT0 product_NN1 as_PRP these_DT0 factors_NN2 may_VM0 relate_VVI to_PRP the_AT0 safety_NN1 or_CJC effectiveness_NN1 of_PRF the_AT0 product_NN1 ._SENT This_DT0 notification_NN1 should_VM0 occur_VVI well_AV0 before_PRP making_VVG any_DT0 changes_NN2 to_TO0 permit_VVI authorized_AJ0 parties_NN2 to_TO0 submit_VVI application_NN1 changes_NN2 within_PRP an_AT0 appropriate_AJ0 time_NN1 frame_NN1 ._SENT For_PRP additional_AJ0 information_NN1 on_PRP DMF_NP0 submission_NN1 guidelines_NN2 ,_PUN refer_VVB to_PRP 21_CRD CFR_NP0 314.420_CRD ,_PUN 21_CRD CFR_NP0 601.51_CRD (_PUL a_AT0 )_PUR ,_PUN and_CJC the_AT0 draft_NN1 guidance_NN1 for_PRP industry_NN1 Drug_NN1 Master_NP0 Files_NP0 (_PUL October_NP0 2019_CRD )_PUR .12_CRD 
This_DT0 guidance_NN1 is_VBZ not_XX0 intended_VVN to_TO0 alter_VVI existing_AJ0 submission_NN1 processes_NN2 ;_PUN applicants_NN2 should_VM0 follow_VVI the_AT0 recommendations_NN2 in_PRP current_AJ0 guidance_NN1 documents_NN2 for_PRP reporting_VVG CMC_NP0 changes_NN2 to_PRP an_AT0 approved_AJ0 application_NN1 (_PUL see_VVB section_NN1 VII_CRD ._SENT ,_PUN References_NN2 )_PUR ._SENT 
IV_CRD ._SENT Common_AJ0 Changes_NN2 Related_VVN to_PRP Glass_NN1 Vials_NN2 and_CJC Stoppers_NN2 
The_AT0 tables_NN2 in_PRP Appendix_NN1 A_ZZ0 of_PRF this_DT0 guidance_NN1 include_VVB information_NN1 derived_VVN from_PRP existing_AJ0 FDA_NN1 guidance_NN1 documents_NN2 that_CJT contain_VVB recommendations_NN2 for_PRP reporting_VVG category_NN1 and_CJC submission_NN1 content_NN1 related_VVN to_PRP common_AJ0 CMC_NP0 changes_NN2 to_PRP CCS_NP0 components_NN2 (_PUL glass_NN1 vials_NN2 and_CJC stoppers_NN2 )_PUR for_PRP finished_AJ0 drug_NN1 and_CJC biological_AJ0 products_NN2 ._SENT The_AT0 tables_NN2 include_VVB the_AT0 type_NN1 of_PRF data_NN0 recommended_VVN to_TO0 support_VVI a_AT0 specific_AJ0 change_NN1 (_PUL as_CJS discussed_VVN in_PRP the_AT0 guidance_NN1 for_PRP industry_NN1 Container_NN1 Closure_NN1 Systems_NN2 for_PRP Packaging_VVG Human_AJ0 Drugs_NN2 and_CJC Biologics_NN2 ;_PUN Chemistry_NN1 ,_PUN Manufacturing_NN1 ,_PUN and_CJC Controls_NN2 Documentation_NN1 (_PUL May_NP0 1999_CRD )_PUR )_PUR ,_PUN as_CJS well_AV0 as_CJS the_AT0 recommended_AJ0 reporting_NN1 category_NN1 ._SENT Some_DT0 submission_NN1 data_NN0 recommendations_NN2 and_CJC reporting_NN1 categories_NN2 may_VM0 differ_VVI based_VVN on_PRP the_AT0 nature_NN1 of_PRF the_AT0 product_NN1 and_CJC the_AT0 potential_AJ0 risk_NN1 to_PRP product_NN1 quality_NN1 ,_PUN as_CJS it_PNP may_VM0 relate_VVI to_PRP safety_NN1 and_CJC effectiveness_NN1 of_PRF the_AT0 product_NN1 ._SENT The_AT0 quantity_NN1 of_PRF data_NN0 that_CJT should_VM0 be_VBI included_VVN in_PRP the_AT0 submission_NN1 depends_VVZ on_PRP the_AT0 application_NN1 type_NN1 and_CJC available_AJ0 body_NN1 of_PRF knowledge.13_AJ0 Changes_NN2 should_VM0 be_VBI supported_VVN with_PRP confirmatory14_CRD batch_NN1 data_NN0 ._SENT To_TO0 assess_VVI the_AT0 change_NN1 ,_PUN FDA_NP0 may_VM0 request_VVI that_CJT the_AT0 applicant_NN1 provide_VVB additional_AJ0 information_NN1 in_PRP the_AT0 supplement_NN1 or_CJC referenced_VVD DMF_NP0 ._SENT 
An_AT0 applicant_NN1 seeking_VVG to_TO0 make_VVI more_AV0 than_CJS one_CRD related_AJ0 change_NN1 concurrently_AV0 should_VM0 submit_VVI a_AT0 supplement_NN1 with_PRP data_NN0 appropriate_AJ0 to_TO0 address_VVI the_AT0 potential_AJ0 risk_NN1 from_PRP the_AT0 cumulative_AJ0 effect_NN1 of_PRF multiple_AJ0 changes_NN2 ._SENT Where_CJS the_AT0 recommended_AJ0 reporting_NN1 categories_NN2 for_PRP the_AT0 individual_AJ0 changes_NN2 differ_VVB ,_PUN the_AT0 submission_NN1 category_NN1 selected_VVN should_VM0 be_VBI the_AT0 one_PNI associated_VVN with_PRP the_AT0 highest_AJS risk_NN1 change_NN1 (_PUL e.g._AV0 ,_PUN PAS_NP0 )_PUR of_PRF the_AT0 categories_NN2 recommended_VVN for_PRP the_AT0 individual_AJ0 changes_NN2 ._SENT 
When_CJS the_AT0 CCS_NP0 changes_NN2 described_VVN in_PRP the_AT0 tables_NN2 in_PRP Appendix_NN1 A_ZZ0 necessitate_VVB a_AT0 corresponding_AJ0 change_NN1 in_PRP finished_AJ0 product_NN1 specifications_NN2 ,_PUN 15_CRD the_AT0 applicant_NN1 should_VM0 provide_VVI all_DT0 studies_NN2 and_CJC data_NN0 appropriate_AJ0 to_TO0 support_VVI the_AT0 affected_AJ0 specification_NN1 change_NN1 (_PUL s_ZZ0 )_PUR ._SENT The_AT0 reporting_NN1 category_NN1 depends_VVZ on_PRP the_AT0 potential_NN1 to_TO0 have_VHI an_AT0 adverse_AJ0 effect_NN1 on_PRP the_AT0 identity_NN1 ,_PUN strength_NN1 ,_PUN quality_NN1 ,_PUN purity_NN1 ,_PUN or_CJC potency_NN1 of_PRF the_AT0 product_NN1 as_PRP these_DT0 factors_NN2 may_VM0 relate_VVI to_PRP the_AT0 safety_NN1 or_CJC effectiveness_NN1 of_PRF the_AT0 product_NN1 ._SENT For_PRP example_NN1 ,_PUN tightening_VVG the_AT0 acceptance_NN1 criteria_NN2 for_PRP a_AT0 quality_NN1 attribute_NN1 may_VM0 warrant_VVI a_AT0 lower_AJC reporting_NN1 category_NN1 than_CJS widening_VVG the_AT0 acceptance_NN1 criteria_NN2 ._SENT 
Before_CJS introducing_VVG a_AT0 new_AJ0 CCS_NP0 component_NN1 that_CJT differs_VVZ from_PRP the_AT0 specified_AJ0 CCS_NP0 component_NN1 type_NN1 /_PUN grade_NN1 in_PRP product_NN1 labeling_NN1 (_PUL e.g._AV0 ,_PUN "_PUQ packaged_VVN in_PRP type_NN1 1_CRD glass_NN1 "_PUQ )_PUR ,_PUN a_AT0 supplement_NN1 to_TO0 change_VVI product_NN1 labeling_NN1 may_VM0 be_VBI appropriate_AJ0 ._SENT When_CJS the_AT0 CCS_NP0 new_AJ0 component_NN1 differs_VVZ from_PRP that_DT0 specified_VVN in_PRP the_AT0 applicable_AJ0 USP_NN1 monograph_NN1 ,_PUN appropriate_AJ0 engagement_NN1 with_PRP USP_NN1 regarding_PRP an_AT0 update_NN1 to_PRP the_AT0 product_NN1 monograph16_NN1 may_VM0 be_VBI necessary_AJ0 ._SENT 
V._PRP Tools_NN2 to_TO0 Facilitate_VVB Changes_NN2 to_PRP CCS_NP0 Components_NN2 
For_PRP CCS_NP0 and_CJC component_NN1 changes_NN2 that_CJT are_VBB the_AT0 subject_NN1 of_PRF this_DT0 guidance_NN1 ,_PUN FDA_NP0 intends_VVZ to_TO0 consider_VVI risk-based_AJ0 approaches_NN2 under_PRP existing_AJ0 tools_NN2 and_CJC capabilities_NN2 to_TO0 facilitate_VVI providing_VVG timely_AJ0 feedback_NN1 ,_PUN guidance_NN1 ,_PUN and_CJC assessment17_CRD of_PRF proposed_AJ0 changes_NN2 as_CJS discussed_VVN below_AV0 ._SENT 
FDA_NP0 may_VM0 expedite_VVI the_AT0 assessment_NN1 of_PRF a_AT0 supplement_NN1 or_CJC determine_VVB that_CJT a_AT0 different_AJ0 reporting_NN1 category_NN1 is_VBZ appropriate_AJ0 ,_PUN taking_VVG into_PRP account_NN1 public_AJ0 health_NN1 priorities18_NN1 and_CJC the_AT0 applicant_NN1 's_POS rationale_NN1 and_CJC associated_AJ0 risk_NN1 assessment_NN1 and_CJC mitigation_NN1 strategy_NN1 for_PRP the_AT0 proposed_AJ0 change_NN1 ._SENT Should_VM0 a_AT0 different_AJ0 reporting_NN1 category_NN1 be_VBI determined_VVN to_TO0 be_VBI appropriate_AJ0 ,_PUN FDA_NP0 will_VM0 notify_VVI the_AT0 applicant_NN1 and_CJC convey_VVB its_DPS rationale_NN1 for_PRP the_AT0 determination_NN1 ._SENT 
A_ZZ0 ._SENT Risk-Based_AJ0 Considerations_NN2 for_PRP Supplement_NN1 Reporting_VVG Categories_NN2 
During_PRP this_DT0 public_AJ0 health_NN1 emergency_NN1 ,_PUN FDA_NP0 will_VM0 consider_VVI requests_NN2 to_TO0 submit_VVI certain_AJ0 changes_NN2 to_PRP CCS_NP0 using_VVG a_AT0 lower_AJC reporting_NN1 category_NN1 than_CJS that_DT0 recommended_VVN in_PRP existing_AJ0 guidance_NN1 if_CJS the_AT0 applicants_NN2 are_VBB experiencing_VVG constrained_AJ0 supply_NN1 of_PRF CCS_NP0 or_CJC components_NN2 thereof_AV0 ,_PUN and_CJC if_CJS the_AT0 relevant_AJ0 NDAs_NP0 ,_PUN ANDAs_NP0 ,_PUN or_CJC BLAs_NP0 are_VBB related_VVN to_PRP the_AT0 treatment_NN1 or_CJC prevention_NN1 of_PRF COVID-19_AJ0 or_CJC other_AJ0 drugs_NN2 in_PRP shortage_NN1 ,_PUN as_CJS appropriate_AJ0 ._SENT Consistent_AJ0 with_PRP applicable_AJ0 regulations_NN2 and_CJC existing_AJ0 guidance_NN1 documents_NN2 related_VVN to_PRP postapproval_NN1 CMC_NP0 changes_NN2 for_PRP drug_NN1 applications_NN2 and_CJC BLAs_NP0 ,_PUN FDA_NP0 may_VM0 consider_VVI available_AJ0 information_NN1 and_CJC approaches_VVZ to_TO0 mitigate_VVI the_AT0 risk_NN1 to_PRP product_NN1 quality_NN1 when_CJS determining_VVG whether_CJS a_AT0 lower_AJC reporting_NN1 category_NN1 for_PRP supplements_NN2 is_VBZ appropriate_AJ0 ._SENT Applicants_NN2 wishing_VVG to_TO0 request_VVI a_AT0 lower_AJC supplement_NN1 reporting_NN1 category_NN1 should_VM0 provide_VVI (_PUL 1_CRD )_PUR their_DPS rationale_NN1 ,_PUN 
(_PUL 2_CRD )_PUR supporting_AJ0 information_NN1 ,_PUN and_CJC (_PUL 3_CRD )_PUR risk-mitigation_NN1 approaches_NN2 ,_PUN for_PRP FDA_NN1 to_TO0 consider_VVI whether_CJS the_AT0 requested_AJ0 reduction_NN1 in_PRP reporting_NN1 category_NN1 is_VBZ appropriate_AJ0 ._SENT 
Before_CJS submitting_VVG a_AT0 supplement_NN1 with_PRP a_AT0 lower_AJC reporting_NN1 category_NN1 than_CJS what_DTQ is_VBZ required_VVN in_PRP existing_AJ0 regulations_NN2 and_CJC recommended_VVN in_PRP existing_AJ0 guidance_NN1 ,_PUN applicants_NN2 should_VM0 contact_VVI FDA_NN1 for_PRP feedback_NN1 and_CJC concurrence_NN1 ._SENT For_PRP Center_NN1 for_PRP Drug_NN1 Evaluation_NN1 and_CJC Research_NN1 (_PUL CDER_NP0 )_PUR -regulated_AJ0 products_NN2 ,_PUN applicants_NN2 should_VM0 send_VVI an_AT0 email_NN1 to_PRP replaced-email_NN1 should_VM0 circumstances_NN2 resulting_VVG from_PRP the_AT0 COVID-19_AJ0 pandemic_AJ0 warrant_NN1 the_AT0 use_NN1 of_PRF atypical_AJ0 or_CJC flexible_AJ0 submission_NN1 strategies_NN2 as_CJS described_VVN in_PRP this_DT0 section.19_NN1 For_PRP Center_NN1 for_PRP Biologics_NP0 Evaluation_NN1 and_CJC Research_NN1 (_PUL CBER_NP0 )_PUR -regulated_AJ0 products_NN2 ,_PUN applicants_NN2 should_VM0 contact_VVI the_AT0 appropriate_AJ0 CBER_AJ0 review_NN1 office_NN1 ._SENT Additionally_AV0 ,_PUN if_CJS the_AT0 CDER-_AJ0 or_CJC CBER-regulated_AJ0 product_NN1 could_VM0 enter_VVI ,_PUN or_CJC is_VBZ currently_AV0 in_PRP ,_PUN drug_NN1 shortage_NN1 ,_PUN then_AV0 the_AT0 respective_AJ0 applicant_NN1 should_VM0 include_VVI CDER_AJ0 DRUG_NN1 SHORTAGES_NN2 (_PUL replaced-email_NP0 )_PUR for_PRP products_NN2 regulated_VVN by_PRP CDER_NN1 and_CJC replaced-email_NN1 for_PRP products_NN2 regulated_VVN by_PRP CBER_NP0 on_PRP those_DT0 communications_NN2 ._SENT 
For_PRP more_DT0 information_NN1 ,_PUN refer_VVB to_PRP the_AT0 guidance_NN1 for_PRP industry_NN1 Manufacturing_NN1 ,_PUN Supply_NN1 Chain_NN1 ,_PUN and_CJC Drug_NN1 and_CJC Biological_AJ0 Product_NN1 Inspections_NN2 During_PRP COVID-19_AJ0 Public_AJ0 Health_NN1 Emergency_NN1 ;_PUN Questions_NN2 and_CJC Answers_NN2 ._SENT 
B_ZZ0 ._SENT Comparability_NN1 Protocols_NN2 
As_CJS explained_VVN in_PRP the_AT0 draft_NN1 guidance_NN1 for_PRP industry_NN1 Comparability_NN1 Protocols_NN2 for_PRP Human_AJ0 Drugs_NN2 and_CJC Biologics_NN2 :_PUN Chemistry_NN1 ,_PUN Manufacturing_NN1 ,_PUN and_CJC Controls_NN2 Information_NN1 (_PUL April_NP0 2016_CRD )_PUR ,_PUN 20_CRD a_AT0 comparability_NN1 protocol_NN1 (_PUL CP_NP0 )_PUR is_VBZ a_AT0 comprehensive_AJ0 ,_PUN prospectively_AV0 written_VVN plan_NN1 for_PRP assessing_VVG the_AT0 effect_NN1 of_PRF a_AT0 proposed_AJ0 CMC_NP0 postapproval_NN1 change_NN1 (_PUL s_ZZ0 )_PUR on_PRP the_AT0 identity_NN1 ,_PUN strength_NN1 ,_PUN quality_NN1 ,_PUN purity_NN1 ,_PUN and_CJC potency_NN1 of_PRF a_AT0 drug_NN1 product_NN1 or_CJC a_AT0 biological_AJ0 product_NN1 ._SENT It_PNP is_VBZ a_AT0 tool_NN1 for_PRP applicants_NN2 to_TO0 obtain_VVI feedback_NN1 from_PRP FDA_NN1 on_PRP prospective_AJ0 scientific_AJ0 approaches_NN2 ,_PUN submitted_VVN as_PRP a_AT0 part_NN1 of_PRF an_AT0 original_AJ0 application_NN1 or_CJC PAS_NP0 ,_PUN to_TO0 facilitate_VVI expeditious_AJ0 implementation_NN1 of_PRF postapproval_NN1 changes_NN2 ._SENT CPs_NN0 allow_VVB FDA_NN1 to_TO0 review_VVI a_AT0 description_NN1 of_PRF one_CRD or_CJC more_AV0 proposed_AJ0 CMC_NP0 postapproval_NN1 changes_NN2 ,_PUN supporting_AJ0 information_NN1 (_PUL including_PRP any_DT0 analysis_NN1 and_CJC risk_NN1 assessment_NN1 activities_NN2 )_PUR ,_PUN the_AT0 plan_NN1 for_PRP implementing_VVG the_AT0 change_NN1 (_PUL s_ZZ0 )_PUR ,_PUN and_CJC ,_PUN if_CJS appropriate_AJ0 ,_PUN the_AT0 proposed_AJ0 reduced_AJ0 reporting_NN1 category_NN1 for_PRP the_AT0 change_NN1 (_PUL s_ZZ0 )_PUR ._SENT By_PRP delineating_VVG the_AT0 specific_AJ0 approach_NN1 to_TO0 be_VBI used_VVN to_TO0 evaluate_VVI one_PNI or_CJC more_DT0 future_AJ0 changes_NN2 and_CJC the_AT0 rationale_NN1 for_PRP that_DT0 approach_NN1 ,_PUN the_AT0 applicant_NN1 can_VM0 gain_VVI the_AT0 Agency_NN1 's_POS approval_NN1 of_PRF the_AT0 plan_NN1 well_AV0 in_PRP advance_NN1 of_PRF the_AT0 need_NN1 to_TO0 implement_VVI the_AT0 change_NN1 (_PUL s_ZZ0 )_PUR ._SENT This_DT0 process_NN1 can_VM0 facilitate_VVI a_AT0 more_AV0 efficient_AJ0 submission_NN1 process_NN1 for_PRP the_AT0 applicant_NN1 and_CJC review_NN1 process_NN1 for_PRP FDA_NP0 ._SENT 
If_CJS the_AT0 original_AJ0 application_NN1 or_CJC PAS_NP0 containing_VVG the_AT0 CP_NP0 is_VBZ approved_VVN ,_PUN the_AT0 change_NN1 usually_AV0 can_VM0 be_VBI implemented_VVN under_PRP a_AT0 lower_AJC reporting_NN1 category_NN1 than_CJS would_VM0 normally_AV0 be_VBI expected_VVN based_VVN on_PRP recommendations_NN2 in_PRP guidance_NN1 (_PUL e.g._AV0 ,_PUN changes_NN2 otherwise_AV0 requiring_VVG a_AT0 prior_AJ0 approval_NN1 supplement_NN1 could_VM0 be_VBI implemented_VVN under_PRP a_AT0 CBE-30_CRD )_PUR ._SENT A_AT0 CP_NP0 can_VM0 then_AV0 be_VBI used_VVN for_PRP a_AT0 one-time_AJ0 change_NN1 (_PUL s_ZZ0 )_PUR or_CJC be_VBI used_VVN repeatedly_AV0 for_PRP a_AT0 specified_AJ0 type_NN1 of_PRF change_NN1 over_PRP the_AT0 life_NN1 cycle_NN1 of_PRF a_AT0 product_NN1 ._SENT A_AT0 CP_NP0 can_VM0 also_AV0 be_VBI submitted_VVN to_TO0 cover_VVI an_AT0 identical_AJ0 change_NN1 (_PUL s_ZZ0 )_PUR that_DT0 affects_VVZ multiple_AJ0 applications_NN2 (_PUL grouped_AJ0 supplements_NN2 ,_PUN trans-BLA_NN1 submissions_NN2 )_PUR .21_CRD A_ZZ0 CP_NP0 is_VBZ a_AT0 well-suited_AJ0 tool_NN1 for_PRP making_VVG changes_NN2 to_PRP glass_NN1 vials_NN2 and_CJC stoppers_NN2 ,_PUN because_CJS a_AT0 change_NN1 to_PRP one_CRD component_NN1 can_VM0 be_VBI implemented_VVN to_PRP many_DT0 products_NN2 sharing_VVG that_DT0 container_NN1 or_CJC closure_NN1 ,_PUN and_CJC the_AT0 protocol_NN1 could_VM0 be_VBI used_VVN multiple_AJ0 times_NN2 as_PRP the_AT0 need_NN1 arises_VVZ for_PRP additional_AJ0 changes_NN2 to_TO0 accommodate_VVI the_AT0 dynamic_AJ0 supply_NN1 chain_NN1 evolution_NN1 in_PRP reaction_NN1 to_PRP COVID-19_NN1 ._SENT 
VI_CRD ._SENT Additional_AJ0 Resources_NN2 
For_PRP additional_AJ0 questions_NN2 about_PRP this_DT0 guidance_NN1 ,_PUN contact_NN1 CDER_NN1 at_PRP CDER-OPQ-_AJ0 replaced-email_NN1 ,_PUN or_CJC contact_VVB the_AT0 CBER_AJ0 office_NN1 responsible_AJ0 for_PRP the_AT0 product_NN1 's_POS regulation_NN1 ._SENT The_AT0 text_NN1 "_PUQ COVID-19_AJ0 Container_NN1 Closure_NN1 System_NN1 and_CJC Component_NN1 Changes_NN2 "_PUQ should_VM0 be_VBI included_VVN in_PRP the_AT0 subject_AJ0 line_NN1 of_PRF the_AT0 email_NN1 ._SENT 
