What facility information is involved in the drug application? FDA issues guidelines to clarify
Last Update: 2020-06-19
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During the national day of 2019, FDA refused to accept the inspection and gave a warning because of the refusal of Shanghai Medical Engineering Institute: FDA originally planned to carry out routine inspection and on-site inspection before drug approval for Shanghai Pharmaceutical Industry Research Institute located at 285 Copernicus Road, Pudong District, Shanghai from November 29 to December 4, 2018However, on December 4, 2018, the Shanghai Pharmaceutical Industry Research Institute replied in writing to the FDA China office to reject the pre announced inspection< br / > after the event, the Shanghai Medical Engineering Institute issued a statement explaining that: it said that there was a reason for thisThe statement showed that the reason why the FDA required the on-site inspection of Shanghai Medical Engineering Institute was that the relevant domestic enterprises incorporated the test atlas issued by Shanghai Medical Engineering Institute into the release report of their products, but Shanghai Medical Engineering Institute did not know about this and did not sign relevant agreements with the above enterprises, so it was not suitable for inspection< br / > in October 2019, the FDA issued the guidance identification of manufacturing establishments in applications submitted to CBER and CDER questions and answers, which specifies and guides the specific facilities and information that enterprises need to submit in drug application to FDA< br / > I take the liberty to translate this guide document quickly, hoping to help and promote the application work of domestic enterprisesHere is the translation and introduction of the key points of this FDA guidance document< br / > this document consists of three parts: introduction, background information and Q & AAmong them, the Q & a part includes: the Q & a related to form FDA 356h, the Q & A of module 3, and the Q & A of general nature< br / > the background information section < br / > FDA often receives questions about the expectations of including production facility information in the application (module 3) and FDA 356h formsIn some cases, this lack of clarity leads to the inclusion of irrelevant information, misplaced information (e.g., not easily accessible to FDA reviewers), or a lack of information in applications received by FDAThese problems can cause delays in the evaluation process and, in some cases, unnecessary IR, RTF, and RTR operationsThis guide provides detailed recommendations on the placement of facility information in applications< br / > question and reply part < br / > note: for readers to read, the following numbering sequence is the original one in FDA guide< br / > IIIQ & A < br / > FDA 356h form related Q & A < br / > 1What should be included in the facility information in FDA 356h form? < br / > application, revision, supplement related to therapeutic effect, CMC supplement of original NDA, anda and bla, and resubmission of these submission types The applicant should include complete information of production, packaging and control sites of all drugs and drugs in FDA 356h form This should include: < br / > o production (including internal packaging, packaging and labeling sites) and testing sites (including stability testing sites) of all preparations (central control materials and final products) intended for commercial use Stability test information related to APIs and formulations should be included in module 3 (see below) < br / > o production and testing sites for all intermediates (performing the operations described in ICH Q7 guidelines (September 2016)) and end APIs intended for commercial use These include sterilization and micronization sites < br / > This includes final equipment and facilities and facilities for design control activities, including verification and validation of equipment components For more information on composite products, please refer to the cGMP guidelines for composite products (January 2017) < br / > < br / > 2 Should all facilities in module 2 and module 3 be listed in FDA 356h form? < br / > No Facilities that do not affect or involve a commercial control strategy do not need to be listed in form FDA 356h For examples of these facilities, refer to question 1 in module 3 Q & A < br / > 3 Which facilities should be identified in the facility column of FDA form 356h when submitting the amendment or supplement application? < br / > the documents submitted should include the complete information of the existing facilities and any changes to the previously submitted facility information If the applicant is adding a new facility or removing a previously submitted facility, this information should be recorded on the FDA 356h form and submitted with the revised or supplemental application Check the appropriate box: < br / > status to be applied: new facilities are introduced in the application < br / > activation status: the application has been approved and used < br / > inactive: it is approved for drug production according to the application, but it is not used at present < br / > withdrawal: any facility withdrawn from the current, waiting period, original or supplementary submission < br / > 4 If a facility is cancelled, how should the FDA 356h form be modified? < br / > If an unapproved facility is withdrawn prior to the approval of an application for an additional facility (such as an original or supplementary facility), or if a previously approved facility has been withdrawn in a post approval notice in accordance with 21 CFR 314.70 or 601.12, the facility should remain in the FDA 356h form and check the "withdraw" box For amendment requests, from the first amendment, notify FDA that the facility will be withdrawn, and all subsequent amendments, until the application is withdrawn or approved In the subsequent supplementary application, the cancelled facilities shall be deleted from the list < br / > 5 For combined products, should manufacturers of equipment components be listed? < br / > Yes For combined products, the manufacturing facilities for any finished product unit component intended for commercial product processing shall be listed on the FDA 356h form This includes facilities for design control activities in accordance with 21 CFR 820.30 equipment components, including verification and validation In addition, the FDA 356h form should list the facilities that produce the combination < br / > 6 Should the FDA plant identification number (Fei number) and data universal numbering system (Duns) number be provided for a given facility? If so, how to obtain the Fei number and Duns number, or how to check whether the facility has obtained these identification numbers? < br / > having a Fei number and Duns number will facilitate the application process and facility registration < br / > FDA needs to use the Fei number to process the facility evaluation part of the application evaluation < br / > section 510 of the food, drug and Cosmetic Act states that each initial and annual drug registration shall include a unique facility identifier (UFI) (21 U.S.C 360 (b), (c) and (I)) The FDA's preferred UFI for drug agencies is Duns code, which is assigned and managed by Dun & Bradstreet < br / > 21 CFR 207.21 (a) states that "the registrant must register each facility in the country within 5 natural days of the start of production, repacking, relabeling, or recycling of the drug "< br / > 21 CFR 207.21 (b) states that" registrants must register at each foreign facility before importing or offering to import into the United States drugs manufactured, repacked, relabeled or recycled at that facility " < br / > FDA recommends that the owner or operator obtain a Fei number at the time of registration Although the absence of a Fei number may hinder the schedule for the assessment of the facility information contained in your application, you should not delay the submission of your application because there is no Fei number Instead, you should request a Fei number as soon as possible < br / > to get the Fei number of the gdufa related facility, please email email@example.com 。 < br / > to obtain the Fei number of PDUFA or bsufa related facilities, Please send email firstname.lastname@example.org < br / > your email should include the following data points: < br / > (a) subject: foreign or domestic Fei request (company name) < br / > (b) legal name of the company where the activity is held < br / > (c) address of the company where the activity is held < br / > (d) contact person (name, email, phone number) < br / > (E) activities related to drugs (production, labeling, testing, etc.) < br / > (f) known drugs (APIs, finished drugs, intermediates) < br / > (g) registration with FDA (if yes, including registration number) < br / > note: Fei number is a facility specific identifier Therefore, if a facility has been assigned a Fei number (by registering any merchandise, gdufa, PDUFA, bsufa, etc.), you should not ask for a second Fei number for that location < br / > to get Duns number: < br / > o you can get or modify Duns number through Dun & Bradstreet's website: < br / > < br / > o to find or verify the previously obtained Fei or Duns number, please visit the FDA's drug registration website: < br / > < br / > 7 If a facility is listed in the FDA 356h form or other place of application, Does it charge user fees? < br / > the FDA 356h form has nothing to do with the allocation of user fees The function performed by the facility determines the evaluation of user fees, rather than including the facility in the FDA 356h form < br / > if you have any questions about the user fee evaluation, please refer to the various guides for the relevant user fee plan: gdufa, PDUFA, mdufa and bsufa < br / > note: for the application of PDUFA and bsufa, the production facilities / sites mentioned in NDAs and Blas will not charge the user fee since October 1, 2017 < br / > module 3 related Q & A < br / > 1 What facility information should be listed in module 3? < br / > module 3 should include all facilities listed in the FDA 356h form, as well as the R & D, production and testing sites supporting the data generated in the application This includes facilities to produce or test any batch of products < br / > module 3 shall include all facilities listed in the FDA 356h form, as well as research and development, production and testing sites supporting the data generated in the application This includes facilities to produce or test any batch of products < br / > module 3 shall also include a testing laboratory that performs functions related to control strategies, including but not limited to molecular characteristics, similarity and analytical similarity This includes testing sites that generate release data, stability testing sites that support applications, and commercial testing sites < br / > only applicable to combined products: < br / > o provide a detailed list of all production facilities; activities occurred on site (such as assembly and filling, sterilization, testing, etc.); and what components there are on site (for example, only drugs, only equipment, drugs and equipment) For each plant with at least two different component manufacturing operations (e.g., drugs and equipment), determine which cGMP operating system to establish on site in accordance with 21 CFR 4.4 (a) < br / > O for single entity or combined packaging products that need to comply with 21 CFR Part 4, each manufacturing facility needs to determine which cGMP operating system approach is established < br / > o if the cGMP operating system complies with 21 CFR 4.4 (b), determine the method of choice (i.e., 21 CFR 4.4 (b) (1) is fully compliant with 21 CFR 211 and the additional 21 CFR 820, or 21 CFR 4.4 (b) (2) is fully compliant with 21 CFR 820 and the additional CFR 211) < br / > module 3 shall also include a testing laboratory that performs functions related to control strategies, including but not limited to molecular characteristics, similarity and analytical similarity This includes testing sites that generate release data, stability testing sites that support applications, and commercial testing sites < br / > only applicable to combined products: < br / > o provide a detailed list of all production facilities; activities occurred on site (such as assembly and filling, sterilization, testing, etc.); and what components there are on site (for example, only drugs, only equipment, drugs and equipment) For each plant with at least two different component manufacturing operations (e.g., drugs and equipment), determine which cGMP operating system to establish on site in accordance with 21 CFR 4.4 (a) < br / > o each manufacturing facility requires
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