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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Filing Review June 14, 2010 - Isoplate Solution

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Initial Quality Assessment
Branch IV
Division of New Drug Quality Assessment II

Division:

CBER, Division of Blood Applications

NDA:

090067

Applicant:

B. Braun  Medical

Stamp Date:

14 June 2010

PDUFA Date:

14 April 2011

Trade Name:

Isoplate Solution

Established Name:

Multiple Electrolyte Solution

Dosage Form:

Solution

Route of Administration:

Intravenous

Indication:

Platelet additive solution for the storage of leukoreduced hyper concentrated apheresis platelets

 

 

Review Chemist:

Minerva Hughes, PhD

Team Lead:

Moo-Jhong Rhee, PhD

 

 

ONDQA Fileability:

Yes

No

 

 

 

Comments for 74-Day Letter:

 

 

Summary and Critical Issues:

  1. Summary

Pursuant to Section 505(b)(1) of the Federal food, Drug and Cosmetic Act,  B. Braun Medical has submitted NDA 090067 for the use of Isoplate Solution as a platelet additive solution for the storage of leukoreduced hyperconcentrated apheresis platelets collected on CaridianBCT’s Trima Accel System under standard blood banking conditions. The CaridianBCT device is the subject of a pending 510(k) application. 

Isoplate Solution is a sterile, nonpyrogenic, mult-electrolyte solution (pH 7.4) for intravenous use.  The drug product consists of the active ingredients sodium chloride USP (0.53%), sodium acetate trihydrate USP (0.37%), potassium chloride USP (0.037%), magnesium chloride USP (0.03%), sodium phosphate dibasic heptahydrate USP (0.012%), potassium phosphate monobasic NF (0.0082%), sodium gluconate USP (0.5%), and inactive ingredients glacial acetic acid, sodium hydroxide, and water packaged in B. Braun’s EXCEL Container.  

Isoplate Solution is identical in formulation, packaging, sterilization and manufacturing as B. Bruan’s approved Isolyte S, pH 7.4 solution for injection (NDA 19-696), which has been marketed since 1989.  NDA 19-696 was transferred to the Office of Generics in 1997 and is maintained as ANDA 19-696.  The only difference between Isoplate Solution and Isolyte S, pH 7.4 is a change in indication. 

For ease of review, complete manufacturing information is provided in Module 3, with references to DMFs where appropriate. 

  1. Critical Issues for Review

The applicant purports that there are no changes to approved chemistry, manufacturing, and controls (CMC) for Isolyte S, pH 7.4, with the exception of the name and indication change.  The comparability of Isoplate Solution to Isolyte S, pH 7.4 should be verified and the suitability of the product for its proposed new use assessed.  

  1. Comments for 74-Day Letter

The following comments should be conveyed to the sponsor.

    1. DMF letter of authorizations should reference the DMF number, the specific item being referenced, and the date of the submission for that item.  Provide revised DMF letter of authorizations for the ---(b)(4)--- Sodium Chloride USP and Potassium Chloride USP drug substances.  The Agency is unable to review the referenced DMFs in support of your NDA in the absence of an adequate letter of authorization.

       
  1. Comments/Recommendation

From a CMC perspective, the application is fileable.  All pertinent information appears to be included for review.

NDA Number:  
090067

Supplement Number and Type:
N/A

Established/Proper Name:
Multiple Electrolyte Solution

Applicant:
B. Braun Medical

Letter Date:
9 June 2010

Stamp Date:
14 June 2010

The following parameters are necessary in order to initiate a full review, i.e., complete enough to review but may have deficiencies.  On initial overview of the NDA application for filing:

  1. GENERAL

 

Parameter

Yes

No

Comment

  1.  

Is the CMC section organized adequately?

 

 

  1.  

Is the CMC section indexed and paginated (including all PDF files) adequately?

 

 

  1.  

Are all the pages in the CMC section legible?

 

 

  1.  

Has all information requested during the IND phase, and at the pre-NDA meetings been included?

 

 

 

  1. FACILITIES*

 

Parameter

Yes

No

Comment

  1.  

Is a single, comprehensive list of all involved facilities available in one location in the application?

 

 

  1.  

For a naturally-derived API only, are the facilities responsible for critical intermediate or crude API manufacturing, or performing upstream steps, specified in the application?  If not, has a justification been provided for this omission?  This question is not applicable for synthesized API.

 

 

Not applicable

  1.  

Are drug substance manufacturing sites identified on FDA Form 356h or associated continuation sheet?  For each site, does the application list:

    • Name of facility,
    • Full address of facility including street, city, state, country
    • FEI number for facility (if previously registered with FDA)
    • Full name and title, telephone, fax number and email for on-site contact person.
    • Is the manufacturing responsibility and function identified for each facility?, and
    • DMF number (if applicable)

 

 

  1.  

Are drug product manufacturing sites identified on FDA Form 356h or associated continuation sheet.  For each site, does the application list:

    • Name of facility,
    • Full address of facility including street, city, state, country
    • FEI number for facility (if previously registered with FDA)
    • Full name and title, telephone, fax number and email for on-site contact person.
    • Is the manufacturing responsibility and function identified for each facility?, and
    • DMF number (if applicable)

 

 

  1.  

Are additional manufacturing, packaging and control/testing laboratory sites identified on FDA Form 356h or associated continuation sheet. For each site, does the application list:

    • Name of facility,
    • Full address of facility including street, city, state, country
    • FEI number for facility (if previously registered with FDA)
    • Full name and title, telephone, fax number and email for on-site contact person.
    • Is the manufacturing responsibility and function identified for each facility?, and
    • DMF number (if applicable)

 

 

  1.  

Is a statement provided that all facilities are ready for GMP inspection at the time of submission?

 

 

*    If any information regarding the facilities is omitted, this should be addressed ASAP with the applicant and can be a potential filing issue or a potential review issue.

  1. ENVIRONMENTAL ASSESMENT

 

Parameter

Yes

No

Comment

  1.  

Has an environmental assessment report or categorical exclusion been provided?

 

Request for categorical exclusion based on 21 CFR 25.31

 

  1. DRUG SUBSTANCE/ACTIVE PHARMACEUTICAL INGREDIENT (DS/API)

 

Parameter

Yes

No

Comment

  1.  

Does the section contain a description of the DS manufacturing process?

 

There are 7 APIs, all salts of compendial grade.  Information is included if available, otherwise referenced to DMFs and ANDA 019696

  1.  

Does the section contain identification and controls of critical steps and intermediates of the DS?

 

Same as above

  1.  

Does the section contain information regarding the characterization of the DS?

 

Same as above

  1.  

Does the section contain controls for the DS?

 

Same as above

  1.  

Has stability data and analysis been provided for the drug substance?

 

Same as above

  1.  

Does the application contain Quality by Design (QbD) information regarding the DS?

 

Not a filing issue

  1.  

Does the application contain Process Analytical Technology (PAT) information regarding the DS?

 

Not a filing issue

 

  1. DRUG PRODUCT (DP)

 

Parameter

Yes

No

Comment

  1.  

Is there a description of manufacturing process and methods for DP production through finishing, including formulation, filling, labeling and packaging?

 

 

  1.  

Does the section contain identification and controls of critical steps and intermediates of the DP, including analytical procedures and method validation reports for assay and related substances if applicable?

 

 

  1.  

Is there a batch production record and a proposed master batch record?

 

 

  1.  

Has an investigational formulations section been provided?  Is there adequate linkage between the investigational product and the proposed marketed product?

 

Investigational formula is the same as approved ANDA product. 

  1.  

Have any biowaivers been requested?

 

Not needed

  1.  

Does the section contain a description of the to-be-marketed container/closure system and presentations?

 

 

  1.  

Does the section contain controls of the final drug product?

 

 

  1.  

Has stability data and analysis been provided to support the requested expiration date?

 

 

  1.  

Does the application contain Quality by Design (QbD) information regarding the DP?

 

Not a filing issue

  1.  

Does the application contain Process Analytical Technology (PAT) information regarding the DP?

 

Not a filing issue

 

  1. METHODS VALIDATION (MV)

 

Parameter

Yes

No

Comment

  1.  

Is there a methods validation package?

 

 

 

  1. MICROBIOLOGY

 

Parameter

Yes

No

Comment

  1.  

If appropriate, is a separate microbiological section included assuring sterility of the drug product?

 

Product sterility and validation of the sterilization process is included in appropriate DP sections.  Applicant uses parametric release for product sterility control, which was recently approved for the ANDA.

 

  1. MASTER FILES (DMF/MAF)

 

Parameter

Yes

No

Comment

  1.  

Is information for critical DMF references (i.e., for drug substance and important packaging components for non-solid-oral drug products) complete?

 

 

 

DMF #

TYPE

HOLDER

ITEM REFERENCED

LOA DATE

COMMENTS

N/A

II

---(b)(4)---

(b)(4), Sodium Chloride USP

23 Mar 2009

LOA is not adequate. No DMF number or reference to sponsor is given in letter.

N/A

II

---(b)(4)---

(b)(4)--, Potassium Chloride USP

23 Feb 2009

LOA is not adequate. No DMF number or reference to sponsor is given in letter.

(b)(4)

II

---(b)(4)-------

(b)(4)---, Sodium Gluconate USP

9 April 2009

 

(b)(4)

III

---(b)(4)---------------------------------.

---------(b)(4)---------------------------------------------------------------------------------------------------------------

4 Feb 2009

 

(b)(4)

III

---(b)(4)-----

----(b)(4)-----------------------------------------------------------------------------------------------------------------------------------------------------------

23 Jul 2008

 

(b)(4)

III

---(b)(4)------------------.

-----(b)(4)-----------------------------------------------------------------------------------

2 Mar 2010

 

(b)(4)

III

---(b)(4)------

-----(b)(4)---------------------------------------------------

14 Jul 2009

 

(b)(4)

III

---(b)(4)-----------------------------------------

-----(b)(4)---------------------------------------------

15 Dec 2009

 

(b)(4)

III

B. Braun Medical

Qualified Component Vendors

13 April 2010

 

(b)(4)

III

B. Braun Medical

EXCEL® Plastic Container Sterilization Program

15 Dec 2009

 

(b)(4)

III

B. Braun Medical

Material Qualification for
the EXCEL® Plastic

15 Dec 2009

 

(b)(4)

III

B. Braun Medical

Chemistry, Manufacturing and Controls for the EXCEL® Plastic Container

15 Dec 2009

 

(b)(4)

III

B. Braun Medical

Vapor Transmission Studies for the EXCEL® Plastic Container

15 Dec 2009

 

(b)(4)

III

B. Braun Medical

Ink Qualification Studies for
the EXCEL® Plastic Container

15 Dec 2009

 

(b)(4)

III

B. Braun Medical

Accelerated Studies for the
EXCEL® Plastic Container

15 Dec 2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 
 
   
 
   
  
 
 
     
 
 
 
 
    
  
 
 
 

 
 
   
 
   
  
 
 
     
 
 
 
 
    
  
 
 

 

 

 
 
   
 
   
  
 
 
     
 
 
 
 
    
  
 
 

 

 

 

I.   Labeling
 
 ParameterYesNoComment
32.     Has the draft package insert been provided?  
33.    
Have the immediate container and carton labels been provided?
 
 

 

 

  1. FILING CONCLUSION

 

Parameter

Yes

No

Comment

34. 

IS THE PRODUCT QUALITY SECTION OF THE APPLICATION FILEABLE?

 

 

35. 

If the NDA is not fileable from the product quality perspective, state the reasons and provide filing comments to be sent to the Applicant.

 

 

Not applicable

36. 

Are there any potential review issues to be forwarded to the Applicant for the 74-day letter?

 

Updated LOA for ----(b)(4)---- DMFs.

Approval Signatures:   
­­­­­­­­­­­
_________________________      ___________                                                      
Minerva Hughes, PhD, RAC              Date
Review Chemist, ONDQA/DNDQA II/Branch IV

 

________________________      ____________
Moo-Jhong Rhee, Ph.D.               Date
Branch Chief, ONDQA/DNDQA II/Branch IV