FDA Regarding the Disposal of Johnson & Johnson's Covid-19 Vaccine Stock Produced in Emergent...

Compilation: Zhilin-Jiao

Yesterday, we reported on the FDA's decision to dispose of vaccine stock batches affected by production issues at the Emergent plant

The purpose of this memo is to record the FDA (hereinafter referred to as the agency or us) on certain Janssen AD26.

I.

I.

^{[2] [1]}

A.

In August 2020, the AZ COVID-19 vaccine DS will be produced in Zone 3 of the EMOB factory

In November 2020, Janssen COVID-19 vaccine started production in Zone 2 of the EMOB factory

In order to deal with the increased waste, Emergent implemented certain measures from January 2021 to February 8, 2021

The FDA will return to EMOB from February 9 to 11, 2021 for the second pre-EUA on-site inspection

On March 26, 2021, Janssen notified the FDA that they had detected the AZ COVID-19 vaccine virus in Janssen COVID-19 vaccine DS batch 21003600 (GMP8)

The FDA subsequently actively cooperated with Emergent and Janssen to facilitate the investigation of the root cause of the pollution incident

^[3]

The pollution incident reported on March 26, 2021 finally triggered a due inspection by the Office of Regulatory Affairs (ORA) from April 12 to 20, 2021.

^{[4] [5] [6]}

II.

II.

A.

The following is the FDA's FDA quality evaluation of certain batches produced in Zone 2 of the EMOB factory, and whether these batches are suitable for distribution under the production status of the facility (operations are not in compliance with cGMP)

a.
Ad26.
COV2.
S DS Zone 2 batch 21003124 (GMP5), 21003530 (GMP6), 21003533 (GMP7) and 21003603 (GMP9)

The information provided to the FDA and collected during the inspection in April indicated that the production operations and waste flow procedures for the production of Janssen DS batches GMP 5, 6, 7 and 9 are the same as DS batch GMP8, that is, there is a significant increase in production, and at the same time There is a lack of segregation between culture preparation activities, waste streams and personnel handling waste (see Figure 1 below)
.
The quality of these batches is judged according to the production practice when the culture medium is prepared
.
Therefore, in addition to GMP8, the quality of GMP 5, 6, 7 and 9 batches is also problematic because these batches are produced using the same production practices as GMP8
.
In addition, Janssen could not rule out the possibility of AZ vaccine virus contamination in GMP 5, 6, 7 and 9 batches
.
There is no evidence that vaccine contamination, even a low level of contamination, will not affect the safety and effectiveness of the vaccine
.
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Therefore, the FDA determined that the EMOB facility did not operate in accordance with cGMP requirements during GMP 5-9 batch production, and that batch GMP 5, 6, 7, and 9 failed to meet FDA's quality expectations
.
Therefore, batches of GMP 5, 6, 7 and 9 are not suitable for use because the safety and effectiveness of these batches cannot be guaranteed
.
In addition, any batches made by mixing batches including GMP 5 to 9 and other batches are not suitable for use
.
The Janssen COVID-19 vaccine EUA 27205 will not be modified to include these batches in the scope of authorization
.
In light of this decision, FDA recommends scrapping GMP 5, 6, 7 and 9
.

Figure 1: Timeline related to batches of GMP 5 to 9

b.
Ad26.
COV2.
S DS 2 area 21003042 (GMP2) and 21003117 (GMP4)

For Janssen’s AD26.
COV2.
S DS batches GMP2 and GMP4, CBER has thoroughly reviewed the production status of the EMOB facility during the time period during which these batches were produced and the available information for DS batch testing
.
^[8]

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Based on the conditions in the EMOB facilities during the production of GMP 2 and 4 batches recorded in the unpublished EIR, the FDA has determined that the EMOB facilities did not fully comply with cGMP requirements during the relevant time period
.
However, based on the review of facility records and intermediate process and release test results, the quality of the product produced supports FDA's decision to determine that the product is suitable for use
.

In addition, FDA reviewed the information provided to FDA and collected during FDA inspections of EMOB facilities
.
This includes information on the production operations and waste stream procedures for the production of Janssen DS batch GMP8 in District 3.
The GMP8 batch was found to have cross-contamination with AZ's adenovirus vector vaccine
.
In addition, the FDA also reviewed the intermediate process and release test results of GMP2 and GMP4 batches
.
Based on the review of this information, the FDA concluded that the test results of batches GMP2 and GMP4 were within the specified quality specifications of these batches
.
In addition, GMP2 and GMP4 were produced during the period of low waste production at the EMOB facility, and the medium preparation of these batches was separated from the waste path from the materials in Zone 3 in terms of distance and time
.
In other words, GMP2 and GMP4 are produced before facility capacity is overloaded and waste is transferred to areas that cause cross-contamination
.
In view of all the above, and considering the current COVID-19 public health emergency, the FDA has determined that GMP 2 and 4 batches are suitable for use
.
In light of this decision, GMP 2 and 4 batches comply with EUA standards and will be added to Janssen COVID-19 vaccine EUA 27205 for distribution in the United States and possible export to other countries
.
^[9] In addition, any export conditions for these batches or vaccines produced by these batches are that Janssen and Emergent must agree that the FDA can share all relevant information about batch production with regulatory agencies in countries/regions that may use these batches of vaccines.

.
This will provide the regulatory authorities of the destination country with the necessary relevant information so that they may wish to make their own judgments about the applicability of the two batches in their country
.
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Notes:

Notes:

1.
Emergent is headquartered in Gaithersburg, Maryland, and the EMOB Bayview factory discussed in this memo is located in Baltimore, Maryland
.

1.
Emergent is headquartered in Gaithersburg, Maryland, and the EMOB Bayview factory discussed in this memo is located in Baltimore, Maryland
.

2.
In February 2021, the FDA released the third vaccine EUA (EUA 27205) to prevent COVID-19 caused by SARS-CoV-2
.
EUA allows the distribution of Janssen COVID-19 vaccine in the United States for people 18 years of age and older
.

2.
In February 2021, the FDA released the third vaccine EUA (EUA 27205) to prevent COVID-19 caused by SARS-CoV-2
.
EUA allows the distribution of Janssen COVID-19 vaccine in the United States for people 18 years of age and older
.

3.
Refer to the FDA review on June 10, 2021 "CBER's quality evaluation of batches of GMP 5-9 of JNJ Ad26.
COV2.
S stock solution produced in Zone 2 of the EMOB factory" (FDA review of GMP 5-9 )
.

3.
Refer to the FDA review on June 10, 2021 "CBER's quality evaluation of batches of GMP 5-9 of JNJ Ad26.
COV2.
S stock solution produced in Zone 2 of the EMOB factory" (FDA review of GMP 5-9 )
.

4.
See Form EMOB 483 issued by the FDA on April 20, 2021
.

4.
See Form EMOB 483 issued by the FDA on April 20, 2021
.

5.
See the ORA EMOB Facility Inspection Report (EIR), which was not released on May 14, 2021, which is incorporated into this memo by reference
.

5.
See the ORA EMOB Facility Inspection Report (EIR), which was not released on May 14, 2021, which is incorporated into this memo by reference
.

6.
For more information about batch 8, see FDA review of GMP 5-9
.

6.
For more information about batch 8, see FDA review of GMP 5-9
.

7.
For more information about GMP5, GMP6, GMP7 and GMP9, please refer to FDA's review of GMP5-9
.

7.
For more information about GMP5, GMP6, GMP7 and GMP9, please refer to FDA's review of GMP5-9
.

8.
See the FDA review on June 10, 2021 "CBER's Quality Evaluation of JNJ Ad26.
COV2.
S Stock Solution Batches GMP 2 and 4 Produced in Zone 2 of the EMOB Factory"
.

8.
See the FDA review on June 10, 2021 "CBER's Quality Evaluation of JNJ Ad26.
COV2.
S Stock Solution Batches GMP 2 and 4 Produced in Zone 2 of the EMOB Factory"
.

9.
The FDA points out that only GMP 2 and 4 batches and/or vaccines produced from these batches are authorized, and no other batches contain combined batches of GMP 5 to 9 or any batches that are not authorized under the EUA
.

9.
The FDA points out that only GMP 2 and 4 batches and/or vaccines produced from these batches are authorized, and no other batches contain combined batches of GMP 5 to 9 or any batches that are not authorized under the EUA
.

10.
We recognize that regulatory agencies in other countries/regions may wish to make their own judgments on the applicability of these two batches in their countries/regions, and have full access to the production status of the relevant EMOB facilities during the relevant time period.
All available information
.
The FDA has asked Janssen and Emergent to allow the sharing of confidential industry information and trade secret information with foreign countries who express an interest in importing DS batches of GMP2 and GMP4 or finished products made from these batches
.
After obtaining permission from Janssen and Emergent, the FDA intends to share the analysis of DS batches GMP2 and GMP4 on FDA Form 483, the unpublished EIR and CBER, with regulatory agencies in countries expressing interest in importing these batches
.
These countries then have full transparency in accessing the FDA to obtain all information about EMOB production issues and the FDA's decision to determine that these batches do not meet cGMP requirements
.
With this information, these countries can make a fully informed decision on whether to import DS batches of GMP2 and GMP4 or products made from these batches
.

10.
We recognize that regulatory agencies in other countries/regions may wish to make their own judgments on the applicability of these two batches in their countries/regions, and have full access to the production status of the relevant EMOB facilities during the relevant time period.
All available information
.
The FDA has asked Janssen and Emergent to allow the sharing of confidential industry information and trade secret information with foreign countries who express an interest in importing DS batches of GMP2 and GMP4 or finished products made from these batches
.
After obtaining permission from Janssen and Emergent, the FDA intends to share the analysis of DS batches GMP2 and GMP4 on FDA Form 483, the unpublished EIR and CBER, with regulatory agencies in countries expressing interest in importing these batches
.
These countries then have full transparency in accessing the FDA to obtain all information about EMOB production issues and the FDA's decision to determine that these batches do not meet cGMP requirements
.
With this information, these countries can make a fully informed decision on whether to import DS batches of GMP2 and GMP4 or products made from these batches
.